Is ACTB p.Ile330Val (c.988A>G) pathogenic?

ACTB p.Ile330Val (c.988A>G) is classified Uncertain significance in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-13). AlphaMissense: likely benign (0.1473); Very rare (popmax 8.48e-05%, nfe).

How common is ACTB p.Ile330Val (c.988A>G) in the general population?

ACTB p.Ile330Val (c.988A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ACTB p.Ile330Val (c.988A>G)?

AlphaMissense predicts likely benign (score 0.1473) — an in-silico prediction, not a clinical call.

ACTB p.Ile330Val

c.988A>G · VCV4895124

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1473 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1473	likely benign
REVEL	0.499	indeterminate
SaProt	LLR -8.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 152 bp · p 0.071 · regional, not allelic
Overall
CADD	23.4	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 8.48e-05% European (non-Finnish) · 1/1,179,920 alleles

Overall 6.2e-05% 1/1,613,882 alleles · very rare exomes 1/1,461,744 · genomes 0/152,138 · joint denominator

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: ACTB
Protein: p.Ile330Val
Coding: c.988A>G
MANE Select: NM_001101
Type: single nucleotide variant
Location: chr7:5527888 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB

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

Similar variants

ACTB p.Ile330fs Likely pathogenic ★ same residue
ACTB p.Ala22Thr Likely pathogenic ★★ same type
ACTB p.Ala7Thr Likely pathogenic ★★ same type
ACTB p.Arg147Cys Pathogenic ★★ same type
ACTB p.Arg183Trp Pathogenic ★★ same type
ACTB p.Arg196Cys Pathogenic ★★ same type
ACTB p.Arg196His Pathogenic ★★ same type
ACTB p.Arg196Leu Likely pathogenic ★★ 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/actb-p-ile330val (accessed [today's date]).

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