Is ACSM3 p.Phe388Val (c.1162T>G) pathogenic?

ACSM3 p.Phe388Val (c.1162T>G) is classified Uncertain significance in ACSM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-07). AlphaMissense: ambiguous (0.4571); Ultra-rare (popmax 0.0231%, amr).

How common is ACSM3 p.Phe388Val (c.1162T>G) in the general population?

ACSM3 p.Phe388Val (c.1162T>G) is ultra-rare (popmax 0.0231%, amr) (gnomAD).

What do computational predictors say about ACSM3 p.Phe388Val (c.1162T>G)?

AlphaMissense predicts ambiguous (score 0.4571) — an in-silico prediction, not a clinical call.

ACSM3 p.Phe388Val

c.1162T>G · rs767483367 · VCV2348798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4571 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4571	ambiguous
REVEL	0.18	moderately benign-leaning
SaProt	LLR -8.23	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.62, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 27 kb · p 0.16 · regional, not allelic
Overall
CADD	22.4	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 0.0231% Admixed American · 13/56,380 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0108%

Overall 0.000814% 13/1,597,308 alleles · ultra-rare

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: ACSM3
Protein: p.Phe388Val
Coding: c.1162T>G
MANE Select: NM_005622
dbSNP: rs767483367
Type: single nucleotide variant
Location: chr16:20786096 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.12

Full ACSM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACSM3 p.Pro291Leu Uncertain significance ★★ ⚠ same type
THUMPD1 p.Arg157Ter Pathogenic ★ same type
THUMPD1 p.Gln44Ter Likely pathogenic ★ same type
THUMPD1 p.Leu114Ter Pathogenic ★ same type
THUMPD1 p.Pro164Ser Pathogenic ★ same type
ACSM3 p.Ala139Thr Uncertain significance ★ ⚠ same type
ACSM3 p.Ala183Thr Uncertain significance ★ ⚠ same type
ACSM3 p.Ala215Val 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/acsm3-p-phe388val (accessed [today's date]).

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