Is ACTMAP p.Arg334Trp (c.1000C>T) pathogenic?

ACTMAP p.Arg334Trp (c.1000C>T) is classified Uncertain significance in ACTMAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.1522); Ultra-rare (popmax 0.0765%, nfe).

How common is ACTMAP p.Arg334Trp (c.1000C>T) in the general population?

ACTMAP p.Arg334Trp (c.1000C>T) is ultra-rare (popmax 0.0765%, nfe) (gnomAD).

What do computational predictors say about ACTMAP p.Arg334Trp (c.1000C>T)?

AlphaMissense predicts likely benign (score 0.1522) — an in-silico prediction, not a clinical call.

ACTMAP p.Arg334Trp

c.1000C>T · rs200386941 · VCV3141704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1522 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0765%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1522	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -8.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.49, phastCons 0.11
Regional constraint	o/e 1.03	unconstrained · MANE · 7,367 bp · p 0.5 · regional, not allelic
Overall
CADD	23.9	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 0.0765% European (non-Finnish) · 859/1,123,192 alleles

Filtering AF 0.0722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0705%

Overall 0.06% 903/1,504,454 alleles · ultra-rare exomes 850/1,352,212 · genomes 53/152,242 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0765%	1,308
Remaining individualsnot grpmax-eligible	0.0448%	2,233
Middle Eastern	0.0174%	5,732
African / African-American	0.0152%	6,565
East Asian	0.0122%	8,198
Admixed American	0.00217%	45,986

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.Arg334Trp
Coding: c.1000C>T
MANE Select: NM_198476
dbSNP: rs200386941
Type: single nucleotide variant
Location: chr19:40742489 (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.Pro151Ser Uncertain significance ★ ⚠ same type
ACTMAP p.Thr165Met Uncertain significance ★ ⚠ same type
ACTMAP p.Val327Met 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-arg334trp (accessed [today's date]).

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