Is IDS p.Ser117Phe (c.350C>T) pathogenic?

IDS p.Ser117Phe (c.350C>T) is classified Uncertain significance in IDS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-21). AlphaMissense: ambiguous (0.4615); Very rare (popmax 0.000338%, nfe).

How common is IDS p.Ser117Phe (c.350C>T) in the general population?

IDS p.Ser117Phe (c.350C>T) is very rare (popmax 0.000338%, nfe) (gnomAD).

What do computational predictors say about IDS p.Ser117Phe (c.350C>T)?

AlphaMissense predicts ambiguous (score 0.4615) — an in-silico prediction, not a clinical call.

IDS p.Ser117Phe

c.350C>T · rs2520895937 · VCV2577240

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4615 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000338%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4615	ambiguous
REVEL	0.84	moderately pathogenic-leaning
SaProt	LLR -11.91	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.07	constrained · MANE · 819 bp · p 6.4e-10 · regional, not allelic
Overall
CADD	25.4	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 0.000338% European (non-Finnish) · 3/887,858 alleles

Filtering AF 9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000251% 3/1,197,070 alleles · very rare exomes 3/1,083,795 · genomes 0/113,275 · joint denominator

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.Ser117Phe
Coding: c.350C>T
MANE Select: NM_000202
dbSNP: rs2520895937
Type: single nucleotide variant
Location: chrX:149503380 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 117: a UniProt-annotated variant site (in mps2; severe form); a UniProt-annotated variant site (in mps2; severe form; deleterious mutation; results in an inactive enzyme)

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

Similar variants

IDS p.Ser117Tyr Likely pathogenic ★ same residue
IDS p.Ser117del Pathogenic ★ same residue
IDS c.1006+1G>C Pathogenic ★★ same type
IDS c.1006+1G>T Pathogenic ★★ same type
IDS c.1007-133A>G Likely pathogenic ★★ same type
IDS c.1007-1G>A Pathogenic ★★ same type
IDS c.1007-2A>C Pathogenic/Likely pathogenic ★★ same type
IDS c.1007-8T>G Pathogenic/Likely pathogenic ★★ same type

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-ser117phe (accessed [today's date]).

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