Is ACTB p.Val103Leu (c.307G>C) pathogenic?

ACTB p.Val103Leu (c.307G>C) is classified Conflicting classifications of pathogenicity in ACTB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-02-03). AlphaMissense: likely pathogenic (0.7111); Absent from gnomAD v4.1; Associated with Baraitser-Winter cerebrofrontofacial syndrome.

What condition is associated with ACTB p.Val103Leu (c.307G>C)?

ACTB p.Val103Leu (c.307G>C) is associated with Baraitser-Winter cerebrofrontofacial syndrome, Baraitser-Winter syndrome 1 (ClinVar).

How common is ACTB p.Val103Leu (c.307G>C) in the general population?

ACTB p.Val103Leu (c.307G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTB p.Val103Leu (c.307G>C)?

AlphaMissense predicts likely pathogenic (score 0.7111) — an in-silico prediction, not a clinical call.

ACTB p.Val103Leu

c.307G>C · rs587779772 · VCV127165

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7111 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Baraitser-Winter cerebrofrontofacial syndrome

Computational evidence

Protein change
AlphaMissense	0.7111	likely pathogenic
REVEL	0.52	indeterminate
SaProt	LLR -13.27	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.72, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 180 bp · p 1.4e-19 · regional, not allelic
Overall
CADD	26.7	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.Val103Leu
Coding: c.307G>C
MANE Select: NM_001101
dbSNP: rs587779772
Type: single nucleotide variant
Location: chr7:5529217 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 103: a β-strand

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

Disease context

Baraitser-Winter cerebrofrontofacial syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Baraitser-Winter syndrome 1

Similar variants

ACTB p.Val103Met Uncertain significance ★ ⚠ same residue
ACTB p.Ala22Thr Likely pathogenic ★★ same condition
ACTB p.Ala7Thr Likely pathogenic ★★ same condition
ACTB p.Arg147Cys Pathogenic ★★ same condition
ACTB p.Arg183Trp Pathogenic ★★ same condition
ACTB p.Arg196Cys Pathogenic ★★ same condition
ACTB p.Arg196His Pathogenic ★★ same condition
ACTB p.Arg196Leu Likely pathogenic ★★ 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-val103leu (accessed [today's date]).

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