Is ACTG2 p.Val160Leu (c.478G>C) pathogenic?

ACTG2 p.Val160Leu (c.478G>C) is classified Uncertain significance in ACTG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely pathogenic (0.9924); Very rare (popmax 8.49e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ACTG2 p.Val160Leu (c.478G>C)?

ACTG2 p.Val160Leu (c.478G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ACTG2 p.Val160Leu (c.478G>C) in the general population?

ACTG2 p.Val160Leu (c.478G>C) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about ACTG2 p.Val160Leu (c.478G>C)?

AlphaMissense predicts likely pathogenic (score 0.9924) — an in-silico prediction, not a clinical call.

ACTG2 p.Val160Leu

c.478G>C · VCV3483589

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9924 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9924	likely pathogenic
REVEL	0.891	moderately pathogenic-leaning
SaProt	LLR -13.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 18 kb · p 3.5e-30 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.49e-05% European (non-Finnish) · 1/1,177,980 alleles

Overall 0.00106% 17/1,610,862 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.044%	2,275
Remaining individualsnot grpmax-eligible	0.00481%	20,774
European (non-Finnish)grpmax	8.49e-05%	1,177,980

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ACTG2
Protein: p.Val160Leu
Coding: c.478G>C
MANE Select: NM_001615
Type: single nucleotide variant
Location: chr2:73913511 (GRCh38)
Gene constraint: LOEUF 0.626 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 95.46 · 4 PDB

Full ACTG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACTG2 p.Arg178Leu Pathogenic ★★ same condition
ACTG2 p.Ala221Val Uncertain significance ★ ⚠ same condition
ACTG2 p.Asn253Ser Uncertain significance ★ ⚠ same condition
ACTG2 p.His102Tyr Uncertain significance ★ ⚠ same condition
ACTG2 p.His88Arg Uncertain significance ★ ⚠ same condition
ACTG2 p.Ile330Met Uncertain significance ★ ⚠ same condition
ACTG2 p.Lys374Arg Uncertain significance ★ ⚠ same condition
ACTG2 p.Pro71Arg Uncertain significance ★ ⚠ same condition

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/actg2-p-val160leu (accessed [today's date]).

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