Is IDS p.Pro371Leu (c.1112C>T) pathogenic?

IDS p.Pro371Leu (c.1112C>T) is classified Likely benign in IDS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-25). AlphaMissense: likely benign (0.0726); Very rare (popmax 0.00886%, eas); Associated with Inborn genetic diseases.

What condition is associated with IDS p.Pro371Leu (c.1112C>T)?

IDS p.Pro371Leu (c.1112C>T) is associated with Inborn genetic diseases, mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Pro371Leu (c.1112C>T) in the general population?

IDS p.Pro371Leu (c.1112C>T) is very rare (popmax 0.00886%, eas) (gnomAD).

What do computational predictors say about IDS p.Pro371Leu (c.1112C>T)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

IDS p.Pro371Leu

c.1112C>T · rs782471629 · VCV771557

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00886%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.392	indeterminate
SaProt	LLR -5.48	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.12, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	6.229	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00886% East Asian · 3/33,859 alleles

Filtering AF 0.00235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00125%

Overall 0.00198% 24/1,211,794 alleles · very rare exomes 24/1,097,937 · genomes 0/113,857 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00886%	11,286
Admixed American	0.00434%	23,046
South Asian	0.00351%	28,503
Remaining individualsnot grpmax-eligible	0.0021%	47,652
European (non-Finnish)	0.00179%	55,958

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: IDS
Protein: p.Pro371Leu
Coding: c.1112C>T
MANE Select: NM_000202
dbSNP: rs782471629
Type: single nucleotide variant
Location: chrX:149486993 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 371: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mucopolysaccharidosis type 2

Similar variants

IDS p.Pro371Ser Uncertain significance ★ ⚠ same residue
IDS p.Pro371= Benign ★ same residue
IDS p.Pro371fs Likely pathogenic ★ same residue
IDS c.1006+1G>C Pathogenic ★★ same condition
IDS c.1006+1G>T Pathogenic ★★ same condition
IDS c.1007-133A>G Likely pathogenic ★★ same condition
IDS c.1007-1G>A Pathogenic ★★ same condition
IDS c.1007-2A>C Pathogenic/Likely 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/ids-p-pro371leu (accessed [today's date]).

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