Is ACSM5 p.Arg157Trp (c.469C>T) pathogenic?

ACSM5 p.Arg157Trp (c.469C>T) is classified Uncertain significance in ACSM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-15). AlphaMissense: ambiguous (0.552); Rare (popmax 0.28%, mid).

How common is ACSM5 p.Arg157Trp (c.469C>T) in the general population?

ACSM5 p.Arg157Trp (c.469C>T) is rare (popmax 0.28%, mid) (gnomAD).

What do computational predictors say about ACSM5 p.Arg157Trp (c.469C>T)?

AlphaMissense predicts ambiguous (score 0.552) — an in-silico prediction, not a clinical call.

ACSM5 p.Arg157Trp

c.469C>T · VCV3263271

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.552 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.28%, mid)

Computational evidence

Protein change
AlphaMissense	0.552	ambiguous
REVEL	0.32	indeterminate
SaProt	LLR -9.88	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -1.5
Regional constraint	o/e 1.00	unconstrained · MANE · 29 kb · p 0.91 · regional, not allelic
Overall
CADD	24.8	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 0.28% Middle Eastern · 17/6,062 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.00725% 117/1,614,082 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.28%	357
Ashkenazi Jewishnot grpmax-eligible	0.111%	897
Admixed American	0.0383%	2,609
Remaining individualsnot grpmax-eligible	0.0192%	5,209
European (non-Finnish)	0.00237%	42,144
East Asian	0.00223%	44,876
South Asian	0.0022%	45,539
African / African-American	0.00133%	74,990

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: ACSM5
Protein: p.Arg157Trp
Coding: c.469C>T
MANE Select: NM_017888
Type: single nucleotide variant
Location: chr16:20419281 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.58

Full ACSM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSM5 p.Pro144Leu Uncertain significance ★★ ⚠ same type
ACSM5 c.1001+10G>A Benign ★★ same type
ACSM5 p.His360Arg Benign ★★ same type
ACSM5 p.Ala160Val Uncertain significance ★ ⚠ same type
ACSM5 p.Ala163Ser Uncertain significance ★ ⚠ same type
ACSM5 p.Arg100Ser Uncertain significance ★ ⚠ same type
ACSM5 p.Arg197Trp Uncertain significance ★ ⚠ same type
ACSM5 p.Arg208Trp Uncertain significance ★ ⚠ 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/acsm5-p-arg157trp (accessed [today's date]).

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