Is ACTB p.Ile71Met (c.213C>G) pathogenic?

ACTB p.Ile71Met (c.213C>G) is classified Uncertain significance in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely pathogenic (0.6617); Absent from gnomAD v4.1.

How common is ACTB p.Ile71Met (c.213C>G) in the general population?

ACTB p.Ile71Met (c.213C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTB p.Ile71Met (c.213C>G)?

AlphaMissense predicts likely pathogenic (score 0.6617) — an in-silico prediction, not a clinical call.

ACTB p.Ile71Met

c.213C>G · rs752744378 · VCV1301337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6617 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6617	likely pathogenic
REVEL	0.689	pathogenic-leaning
SaProt	LLR -9.77	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -4.3
Regional constraint	o/e 0.00	constrained · MANE · 180 bp · p 1.4e-19 · regional, not allelic
Overall
CADD	22.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACTB
Protein: p.Ile71Met
Coding: c.213C>G
MANE Select: NM_001101
dbSNP: rs752744378
Type: single nucleotide variant
Location: chr7:5529311 (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.Ile71= Likely benign ★ 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-ile71met (accessed [today's date]).

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