Is IDUA p.Pro385Ser (c.1153C>T) pathogenic?

IDUA p.Pro385Ser (c.1153C>T) is classified Uncertain significance in IDUA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-26). AlphaMissense: likely pathogenic (0.6136); Ultra-rare (popmax 0.0141%, sas); Associated with IDUA-related disorder.

What condition is associated with IDUA p.Pro385Ser (c.1153C>T)?

IDUA p.Pro385Ser (c.1153C>T) is associated with IDUA-related disorder, mucopolysaccharidosis type 1 (ClinVar).

How common is IDUA p.Pro385Ser (c.1153C>T) in the general population?

IDUA p.Pro385Ser (c.1153C>T) is ultra-rare (popmax 0.0141%, sas) (gnomAD).

What do computational predictors say about IDUA p.Pro385Ser (c.1153C>T)?

AlphaMissense predicts likely pathogenic (score 0.6136) — an in-silico prediction, not a clinical call.

IDUA p.Pro385Ser

c.1153C>T · rs752529809 · VCV2195701

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6136 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0141%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

IDUA-related disorder

Computational evidence

Protein change
AlphaMissense	0.6136	likely pathogenic
REVEL	0.879	moderately pathogenic-leaning
SaProt	LLR -11.01	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.43, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 17 kb · p 0.00042 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0141% South Asian · 12/84,954 alleles

Filtering AF 0.00811% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.000996% 14/1,405,284 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0141%	7,079
Remaining individualsnot grpmax-eligible	0.00166%	60,366
African / African-American	0.00136%	73,332

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.Pro385Ser
Coding: c.1153C>T
MANE Select: NM_000203
dbSNP: rs752529809
Type: single nucleotide variant
Location: chr4:1002449 (GRCh38)
Gene constraint: LOEUF 1.344 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.12 · 11 PDB
Residue 385: an α-helix; a UniProt-annotated variant site (in mps1h)

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

Disease context

IDUA-related disorder

Also linked: mucopolysaccharidosis type 1

Similar variants

IDUA p.Pro385Arg Uncertain significance ★★ ⚠ same residue
SLC26A1 p.Val385Met Likely benign ★ 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-pro385ser (accessed [today's date]).

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