Is IDUA p.Ser271Phe (c.812C>T) pathogenic?

IDUA p.Ser271Phe (c.812C>T) is classified Uncertain significance in IDUA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.1099); Very rare (popmax 0.000854%, nfe); Associated with mucopolysaccharidosis type 1.

What condition is associated with IDUA p.Ser271Phe (c.812C>T)?

IDUA p.Ser271Phe (c.812C>T) is associated with mucopolysaccharidosis type 1 (ClinVar).

How common is IDUA p.Ser271Phe (c.812C>T) in the general population?

IDUA p.Ser271Phe (c.812C>T) is very rare (popmax 0.000854%, nfe) (gnomAD).

How is Mucopolysaccharidosis type 1 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about IDUA p.Ser271Phe (c.812C>T)?

AlphaMissense predicts likely benign (score 0.1099) — an in-silico prediction, not a clinical call.

IDUA p.Ser271Phe

c.812C>T · rs766950553 · VCV640514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1099 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000854%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mucopolysaccharidosis type 1

Computational evidence

Protein change
AlphaMissense	0.1099	likely benign
REVEL	0.285	benign-leaning
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.46	GERP -2.9
Regional constraint	o/e 1.12	unconstrained · MANE · 17 kb · p 0.00042 · regional, not allelic
Overall
CADD	0.669	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000854% European (non-Finnish) · 10/1,170,792 alleles

Filtering AF 0.000432% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000315%

Overall 0.00195% 31/1,591,218 alleles · very rare exomes 26/1,438,990 · genomes 5/152,228 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.028%	3,576
Remaining individualsnot grpmax-eligible	0.00648%	15,423
European (non-Finnish)grpmax	0.000854%	117,079

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: IDUA
Protein: p.Ser271Phe
Coding: c.812C>T
MANE Select: NM_000203
dbSNP: rs766950553
Type: single nucleotide variant
Location: chr4:1002001 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.12 · 11 PDB
Residue 271: an α-helix

Full IDUA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mucopolysaccharidosis type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mucopolysaccharidosis type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

IDUA p.Ser271= Likely benign ★ same residue
IDUA p.Ser271Cys Uncertain significance ⚠ same residue
IDUA c.1190-10C>A Likely pathogenic ★★★ same condition
IDUA c.1190-1G>A Pathogenic ★★★ same condition
IDUA c.1402+1G>A Likely pathogenic ★★★ same condition
IDUA c.1402+1G>T Likely pathogenic ★★★ same condition
IDUA c.1402+2T>G Likely pathogenic ★★★ same condition
IDUA c.1403-1G>T Pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/idua-p-ser271phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown