Is ACTB p.Arg312Ser (c.936G>T) pathogenic?

ACTB p.Arg312Ser (c.936G>T) is classified Likely pathogenic in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-10). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with ACTB-associated syndromic thrombocytopenia.

What condition is associated with ACTB p.Arg312Ser (c.936G>T)?

ACTB p.Arg312Ser (c.936G>T) is associated with ACTB-associated syndromic thrombocytopenia (ClinVar).

How common is ACTB p.Arg312Ser (c.936G>T) in the general population?

ACTB p.Arg312Ser (c.936G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTB p.Arg312Ser (c.936G>T)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

ACTB p.Arg312Ser

Q: How is Actinomyopathy-associated syndromic thrombocytopenia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.936G>T · VCV4857233

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ACTB-associated syndromic thrombocytopenia

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar · top 7% in ACTB
REVEL	0.767	pathogenic-leaning
SaProt	LLR -15.76	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 -0.49	GERP -3.7, phastCons 0.033
Regional constraint	o/e 0.11	constrained · MANE · 1,149 bp · p 1.6e-51 · regional, not allelic
Overall
CADD	21.8	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.Arg312Ser
Coding: c.936G>T
MANE Select: NM_001101
Type: single nucleotide variant
Location: chr7:5528052 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 312: an α-helix

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

Disease context

ACTB-associated syndromic thrombocytopenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Actinomyopathy-associated syndromic thrombocytopenia (Orphanet):

Inheritance: Autosomal dominant

Similar variants

ACTB p.Arg312Gly Uncertain significance ★ ⚠ same residue
ACTB p.Arg312= Likely benign ★ same residue
ACTB p.Ala22Thr Likely pathogenic ★★ same condition
ACTB p.Leu171Phe Pathogenic/Likely pathogenic ★★ same condition
ACTB p.Trp356Ter Likely pathogenic ★ same condition
ACTB p.Glu195Gln Uncertain significance ★ ⚠ same condition
ACTB p.Met283Thr Uncertain significance ★ ⚠ same condition
ACTB p.Met44Ile 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/actb-p-arg312ser (accessed [today's date]).

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