Is ACSM1 p.Phe314Val (c.940T>G) pathogenic?

ACSM1 p.Phe314Val (c.940T>G) is classified Uncertain significance in ACSM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.2498); Very rare (popmax 0.00204%, nfe).

How common is ACSM1 p.Phe314Val (c.940T>G) in the general population?

ACSM1 p.Phe314Val (c.940T>G) is very rare (popmax 0.00204%, nfe) (gnomAD).

What do computational predictors say about ACSM1 p.Phe314Val (c.940T>G)?

AlphaMissense predicts likely benign (score 0.2498) — an in-silico prediction, not a clinical call.

ACSM1 p.Phe314Val

c.940T>G · rs377430734 · VCV2591282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2498 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00204%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2498	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -11.36	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.61	GERP -3.4
Regional constraint	o/e 0.94	unconstrained · MANE · 68 kb · p 0.1 · regional, not allelic
Overall
CADD	6.919	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 0.00204% European (non-Finnish) · 24/1,176,464 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00162% 26/1,609,002 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00204%	49,019
Admixed American	0.00167%	59,884
Remaining individualsnot grpmax-eligible	0.00161%	62,230

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: ACSM1
Protein: p.Phe314Val
Coding: c.940T>G
MANE Select: NM_001318890
dbSNP: rs377430734
Type: single nucleotide variant
Location: chr16:20661846 (GRCh38)
Gene constraint: LOEUF 1.248 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.80

Full ACSM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSM1 p.Lys258Arg Benign ★★ ⚠ same type
ACSM1 p.Ala285Val Uncertain significance ★ ⚠ same type
ACSM1 p.Ala336Val Uncertain significance ★ ⚠ same type
ACSM1 p.Ala37Val Uncertain significance ★ ⚠ same type
ACSM1 p.Ala493Gly Uncertain significance ★ ⚠ same type
ACSM1 p.Ala495Val Uncertain significance ★ ⚠ same type
ACSM1 p.Ala60Pro Uncertain significance ★ ⚠ same type
ACSM1 p.Arg153Gln 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/acsm1-p-phe314val (accessed [today's date]).

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