Is ACTB p.Ser60Asn (c.179G>A) pathogenic?

ACTB p.Ser60Asn (c.179G>A) is classified Likely pathogenic in ACTB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-18). AlphaMissense: likely pathogenic (0.9104); Very rare (popmax 0.00223%, eas); Associated with Abnormal brain morphology.

What condition is associated with ACTB p.Ser60Asn (c.179G>A)?

ACTB p.Ser60Asn (c.179G>A) is associated with Abnormal brain morphology, microcephaly (ClinVar).

How common is ACTB p.Ser60Asn (c.179G>A) in the general population?

ACTB p.Ser60Asn (c.179G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ACTB p.Ser60Asn (c.179G>A)?

AlphaMissense predicts likely pathogenic (score 0.9104) — an in-silico prediction, not a clinical call.

ACTB p.Ser60Asn

c.179G>A · rs755437923 · VCV638167

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9104 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Abnormal brain morphology

Computational evidence

Protein change
AlphaMissense	0.9104	likely pathogenic ✓ concordant with ClinVar
REVEL	0.614	indeterminate
SaProt	LLR -12.74	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 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 180 bp · p 1.4e-19 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 0.00223% East Asian · 1/44,890 alleles

Overall 0.000656% 1/152,374 alleles · very rare

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.Ser60Asn
Coding: c.179G>A
MANE Select: NM_001101
dbSNP: rs755437923
Type: single nucleotide variant
Location: chr7:5529345 (GRCh38)
Gene constraint: LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.31 · 93 PDB
Residue 60: an α-helix

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

Disease context

Abnormal brain morphology — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: microcephaly

Similar variants

ACTB p.Ser60Arg Likely pathogenic ★ same residue
ACTB p.Ser60= Conflicting classifications of pathogenicity ★ 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

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-ser60asn (accessed [today's date]).

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