Is IDS p.Ser149Ala (c.445T>G) pathogenic?

IDS p.Ser149Ala (c.445T>G) is classified Benign/Likely benign in IDS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-13). AlphaMissense: likely benign (0.0853); Rare (popmax 0.14%, mid); Associated with Inborn genetic diseases.

What condition is associated with IDS p.Ser149Ala (c.445T>G)?

IDS p.Ser149Ala (c.445T>G) is associated with Inborn genetic diseases, mucopolysaccharidosis type 3A, mucopolysaccharidosis type 2 (ClinVar).

How common is IDS p.Ser149Ala (c.445T>G) in the general population?

IDS p.Ser149Ala (c.445T>G) is rare (popmax 0.14%, mid) (gnomAD).

What do computational predictors say about IDS p.Ser149Ala (c.445T>G)?

AlphaMissense predicts likely benign (score 0.0853) — an in-silico prediction, not a clinical call.

IDS p.Ser149Ala

c.445T>G · rs146846763 · VCV624448

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0853 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.14%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0853	likely benign
REVEL	0.489	indeterminate
SaProt	LLR -5.46	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 9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 21 kb · p 5.6e-05 · regional, not allelic
Overall
CADD	17.73	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 0.14% Middle Eastern · 6/4,273 alleles

Filtering AF 0.0611% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0432%

Overall 0.019% 223/1,173,739 alleles · rare exomes 204/1,062,475 · genomes 19/111,264 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.14%	712
Ashkenazi Jewishnot grpmax-eligible	0.101%	992
South Asian	0.0658%	1,521
Remaining individualsnot grpmax-eligible	0.0193%	5,172
European (non-Finnish)	0.0168%	5,945
Finnishnot grpmax-eligible	0.00431%	23,182
Admixed American	0.00219%	45,707
African / African-American	0.00178%	56,322

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.Ser149Ala
Coding: c.445T>G
MANE Select: NM_000202
dbSNP: rs146846763
Type: single nucleotide variant
Location: chrX:149501011 (GRCh38)
Structure: AlphaFold pLDDT 93.39 · 2 PDB
Residue 149: a turn

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 3A 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-ser149ala (accessed [today's date]).

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