Is ARPC1B p.Cys26Ser (c.77G>C) pathogenic?

ARPC1B p.Cys26Ser (c.77G>C) is classified Uncertain significance in ARPC1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-16). AlphaMissense: ambiguous (0.4685); Very rare (popmax 0.005%, amr).

How common is ARPC1B p.Cys26Ser (c.77G>C) in the general population?

ARPC1B p.Cys26Ser (c.77G>C) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ARPC1B p.Cys26Ser (c.77G>C)?

AlphaMissense predicts ambiguous (score 0.4685) — an in-silico prediction, not a clinical call.

ARPC1B p.Cys26Ser

c.77G>C · rs139034924 · VCV1934012

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4685 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
AlphaMissense	0.4685	ambiguous
REVEL	0.333	indeterminate
SaProt	LLR -6.73	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 8,771 bp · p 0.0087 · regional, not allelic
Overall
CADD	21.4	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 0.005% Admixed American · 3/59,980 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000372% 6/1,613,828 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,993
African / African-American	0.00133%	74,912
European (non-Finnish)	0.00017%	589,936

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: ARPC1B
Protein: p.Cys26Ser
Coding: c.77G>C
MANE Select: NM_005720
dbSNP: rs139034924
Type: single nucleotide variant
Location: chr7:99386697 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 4 PDB

Full ARPC1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARPC1B c.392+2T>C Pathogenic ★★ same type
ARPC1B c.64+2T>A Pathogenic ★★ same type
ARPC1B p.Ala261= Pathogenic ★★ same type
ARPC1B c.1080+4A>C Uncertain significance ★★ same type
ARPC1B c.170-3C>T Uncertain significance ★★ same type
ARPC1B c.501-5G>A Uncertain significance ★★ same type
ARPC1B p.Ala238Val Uncertain significance ★★ ⚠ same type
ARPC1B p.Ala249Val Uncertain significance ★★ ⚠ 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/arpc1b-p-cys26ser (accessed [today's date]).

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