Is ACTB p.His40Tyr (c.118C>T) pathogenic?

ACTB p.His40Tyr (c.118C>T) is classified Pathogenic/Likely pathogenic in ACTB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-21). AlphaMissense: likely pathogenic (0.757); Absent from gnomAD v4.1; Associated with ACTB-related BAFopathy.

What condition is associated with ACTB p.His40Tyr (c.118C>T)?

ACTB p.His40Tyr (c.118C>T) is associated with ACTB-related BAFopathy (ClinVar).

How common is ACTB p.His40Tyr (c.118C>T) in the general population?

ACTB p.His40Tyr (c.118C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACTB p.His40Tyr (c.118C>T)?

AlphaMissense predicts likely pathogenic (score 0.757) — an in-silico prediction, not a clinical call.

ACTB p.His40Tyr

c.118C>T · rs1373863123 · VCV1177325

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.757 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,548)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ACTB-related BAFopathy

Computational evidence

Protein change
AlphaMissense	0.757	likely pathogenic ✓ concordant with ClinVar
REVEL	0.507	indeterminate
SaProt	LLR -11.54	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.84	donor gain · deltas
Pangolin	Δ0.38	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 289 bp · p 4.5e-15 · regional, not allelic
Overall
CADD	34.0	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

No allele count reported in gnomAD v4.1 (AN 1,611,548). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACTB
Protein: p.His40Tyr
Coding: c.118C>T
MANE Select: NM_001101
dbSNP: rs1373863123
Type: single nucleotide variant
Location: chr7:5529540 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 40: a β-strand

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

Disease context

ACTB-related BAFopathy

Similar variants

ACTB p.His40Gln Uncertain significance ★ ⚠ same residue
ACTB p.Arg183Trp Pathogenic ★★ same condition
ACTB p.Arg206Gly Likely pathogenic ★★ same condition
ACTB p.Val159Ala Likely pathogenic ★★ same condition
ACTB p.Val209Leu Likely pathogenic ★★ same condition
ACTB p.Val209Met Pathogenic/Likely pathogenic ★★ same condition
ACTB p.His101Tyr Uncertain significance ★★ ⚠ same condition
ACTB c.984+1G>A 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-his40tyr (accessed [today's date]).

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