Is ARPC1B p.Ser291Arg (c.873C>A) pathogenic?

ARPC1B p.Ser291Arg (c.873C>A) is classified Uncertain significance in ARPC1B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-22). AlphaMissense: likely pathogenic (0.7682); Ultra-rare (popmax 0.019%, sas).

How common is ARPC1B p.Ser291Arg (c.873C>A) in the general population?

ARPC1B p.Ser291Arg (c.873C>A) is ultra-rare (popmax 0.019%, sas) (gnomAD).

What do computational predictors say about ARPC1B p.Ser291Arg (c.873C>A)?

AlphaMissense predicts likely pathogenic (score 0.7682) — an in-silico prediction, not a clinical call.

ARPC1B p.Ser291Arg

c.873C>A · rs749068155 · VCV1375338

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7682 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.019%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7682	likely pathogenic
REVEL	0.207	benign-leaning
SaProt	LLR -7.48	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.37, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 8,771 bp · p 0.0087 · 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

Grpmax group 0.019% South Asian · 16/84,044 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00968%

Overall 0.00114% 16/1,397,400 alleles · ultra-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: ARPC1B
Protein: p.Ser291Arg
Coding: c.873C>A
MANE Select: NM_005720
dbSNP: rs749068155
Type: single nucleotide variant
Location: chr7:99392760 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 4 PDB
Residue 291: an α-helix

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-ser291arg (accessed [today's date]).

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