Is ACTMAP p.Val327Met (c.979G>A) pathogenic?

ACTMAP p.Val327Met (c.979G>A) is classified Uncertain significance in ACTMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-14). AlphaMissense: likely benign (0.2774); Ultra-rare (popmax 0.0205%, nfe).

How common is ACTMAP p.Val327Met (c.979G>A) in the general population?

ACTMAP p.Val327Met (c.979G>A) is ultra-rare (popmax 0.0205%, nfe) (gnomAD).

What do computational predictors say about ACTMAP p.Val327Met (c.979G>A)?

AlphaMissense predicts likely benign (score 0.2774) — an in-silico prediction, not a clinical call.

ACTMAP p.Val327Met

c.979G>A · rs760939718 · VCV3141720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2774 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0205%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2774	likely benign
REVEL	0.386	indeterminate
SaProt	LLR -8.00	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.6, phastCons 0.98
Regional constraint	o/e 1.03	unconstrained · MANE · 7,367 bp · p 0.5 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0205% European (non-Finnish) · 234/1,139,364 alleles

Filtering AF 0.0184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0175%

Overall 0.0163% 250/1,535,360 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0205%	4,869
Remaining individualsnot grpmax-eligible	0.0185%	5,407
Admixed American	0.00589%	16,967
East Asian	0.00238%	42,054
South Asian	0.00128%	78,058

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: ACTMAP
Protein: p.Val327Met
Coding: c.979G>A
MANE Select: NM_198476
dbSNP: rs760939718
Type: single nucleotide variant
Location: chr19:40742510 (GRCh38)
Structure: AlphaFold pLDDT 83.63

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

Similar variants

ACTMAP p.Ala63Thr Uncertain significance ★ ⚠ same type
ACTMAP p.Arg157Trp Uncertain significance ★ ⚠ same type
ACTMAP p.Arg334Trp Uncertain significance ★ ⚠ same type
ACTMAP p.Pro151Ser Uncertain significance ★ ⚠ same type
ACTMAP p.Thr165Met 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/actmap-p-val327met (accessed [today's date]).

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