Is IDS p.Ala317Asp (c.950C>A) pathogenic?

IDS p.Ala317Asp (c.950C>A) is classified Uncertain significance in IDS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-25). AlphaMissense: likely benign (0.2834); Very rare (popmax 0.0035%, afr); Associated with Inborn genetic diseases.

What condition is associated with IDS p.Ala317Asp (c.950C>A)?

IDS p.Ala317Asp (c.950C>A) is associated with Inborn genetic diseases, mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Ala317Asp (c.950C>A) in the general population?

IDS p.Ala317Asp (c.950C>A) is very rare (popmax 0.0035%, afr) (gnomAD).

What do computational predictors say about IDS p.Ala317Asp (c.950C>A)?

AlphaMissense predicts likely benign (score 0.2834) — an in-silico prediction, not a clinical call.

IDS p.Ala317Asp

c.950C>A · rs374576277 · VCV1492947

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0035%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2834	likely benign
REVEL	0.649	pathogenic-leaning
SaProt	LLR -14.71	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	22.5	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 0.0035% African / African-American · 2/57,122 alleles

Filtering AF 0.00249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00282% 34/1,207,730 alleles · very rare exomes 28/1,095,725 · genomes 6/112,005 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0035%	28,561
European (non-Finnish)	0.00347%	28,808
Remaining individualsnot grpmax-eligible	0.0021%	47,520

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.Ala317Asp
Coding: c.950C>A
MANE Select: NM_000202
dbSNP: rs374576277
Type: single nucleotide variant
Location: chrX:149490370 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 317: 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 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
IDS c.1007-8T>G Pathogenic/Likely pathogenic ★★ same condition
IDS c.103+1G>A Pathogenic ★★ same condition
IDS c.104-2A>G 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-ala317asp (accessed [today's date]).

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