Is IDS p.Pro243Ser (c.727C>T) pathogenic?

IDS p.Pro243Ser (c.727C>T) is classified Benign/Likely benign in IDS (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-29). AlphaMissense: likely benign (0.1329); Ultra-rare (popmax 0.023%, nfe); Associated with Inborn genetic diseases.

What condition is associated with IDS p.Pro243Ser (c.727C>T)?

IDS p.Pro243Ser (c.727C>T) is associated with Inborn genetic diseases, mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Pro243Ser (c.727C>T) in the general population?

IDS p.Pro243Ser (c.727C>T) is ultra-rare (popmax 0.023%, nfe) (gnomAD).

What do computational predictors say about IDS p.Pro243Ser (c.727C>T)?

AlphaMissense predicts likely benign (score 0.1329) — an in-silico prediction, not a clinical call.

IDS p.Pro243Ser

c.727C>T · rs143474305 · VCV457355

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1329 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1329	likely benign
REVEL	0.865	moderately pathogenic-leaning
SaProt	LLR -11.40	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	26.2	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 0.023% European (non-Finnish) · 206/895,049 alleles

Filtering AF 0.0204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0194%

Overall 0.0182% 220/1,209,588 alleles · ultra-rare exomes 196/1,097,643 · genomes 24/111,945 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.02%	98
European (non-Finnish)grpmax	0.023%	4,345
Remaining individualsnot grpmax-eligible	0.00841%	11,886
South Asian	0.00352%	28,416
Finnishnot grpmax-eligible	0.00215%	46,605

Amish 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: IDS
Protein: p.Pro243Ser
Coding: c.727C>T
MANE Select: NM_000202
dbSNP: rs143474305
Type: single nucleotide variant
Location: chrX:149496498 (GRCh38)

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

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-pro243ser (accessed [today's date]).

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