Is ACTRT3 p.Leu103Val (c.307T>G) pathogenic?

ACTRT3 p.Leu103Val (c.307T>G) is classified Uncertain significance in ACTRT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.2711); Very rare (popmax 0.00161%, nfe).

How common is ACTRT3 p.Leu103Val (c.307T>G) in the general population?

ACTRT3 p.Leu103Val (c.307T>G) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about ACTRT3 p.Leu103Val (c.307T>G)?

AlphaMissense predicts likely benign (score 0.2711) — an in-silico prediction, not a clinical call.

ACTRT3 p.Leu103Val

c.307T>G · rs1156883179 · VCV2483520

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2711 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2711	likely benign
REVEL	0.476	indeterminate
SaProt	LLR -10.66	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -4.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,085 bp · p 0.65 · regional, not allelic
Overall
CADD	17.17	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 0.00161% European (non-Finnish) · 19/1,180,028 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.0013% 19/1,461,658 alleles · very 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: ACTRT3
Protein: p.Leu103Val
Coding: c.307T>G
MANE Select: NM_032487
dbSNP: rs1156883179
Type: single nucleotide variant
Location: chr3:169768244 (GRCh38)
Gene constraint: LOEUF 1.242 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.47

Full ACTRT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACTRT3 p.Leu103Phe Uncertain significance ★ ⚠ same residue
ACTRT3 p.Ala108Val Uncertain significance ★ ⚠ same type
ACTRT3 p.Ala257Val Uncertain significance ★ ⚠ same type
ACTRT3 p.Ala315Val Uncertain significance ★ ⚠ same type
ACTRT3 p.Ala318Ser Uncertain significance ★ ⚠ same type
ACTRT3 p.Ala323Thr Uncertain significance ★ ⚠ same type
ACTRT3 p.Arg205Ser Uncertain significance ★ ⚠ same type
ACTRT3 p.Arg25Trp 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/actrt3-p-leu103val (accessed [today's date]).

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