Is ARPC1B p.Asp232Asn (c.694G>A) pathogenic?

ARPC1B p.Asp232Asn (c.694G>A) is classified Conflicting classifications of pathogenicity in ARPC1B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-01-18). AlphaMissense: likely benign (0.0779); Ultra-rare (popmax 0.0999%, afr); Associated with Inborn genetic diseases.

What condition is associated with ARPC1B p.Asp232Asn (c.694G>A)?

ARPC1B p.Asp232Asn (c.694G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ARPC1B p.Asp232Asn (c.694G>A) in the general population?

ARPC1B p.Asp232Asn (c.694G>A) is ultra-rare (popmax 0.0999%, afr) (gnomAD).

What do computational predictors say about ARPC1B p.Asp232Asn (c.694G>A)?

AlphaMissense predicts likely benign (score 0.0779) — an in-silico prediction, not a clinical call.

ARPC1B p.Asp232Asn

c.694G>A · rs149569034 · VCV1367237

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0779 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0999%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0779	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.5	GERP 0.78, phastCons 0.98
Regional constraint	o/e 0.89	unconstrained · MANE · 8,771 bp · p 0.0087 · regional, not allelic
Overall
CADD	20.2	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 0.0999% African / African-American · 75/75,048 alleles

Filtering AF 0.0817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.075%

Overall 0.00632% 102/1,613,448 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0999%	1,001
East Asian	0.0134%	7,476
Admixed American	0.0134%	7,487
South Asian	0.0033%	30,333
Remaining individualsnot grpmax-eligible	0.0016%	62,474
Finnishnot grpmax-eligible	0.00156%	63,946
European (non-Finnish)	0.000678%	147,458

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.Asp232Asn
Coding: c.694G>A
MANE Select: NM_005720
dbSNP: rs149569034
Type: single nucleotide variant
Location: chr7:99391086 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 4 PDB
Residue 232: a turn

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARPC1B p.Asp232Glu Likely benign ★ same residue
ARPC1B p.Ala275Thr Uncertain significance ★★ ⚠ same condition
ARPC1B p.Ala276Thr Uncertain significance ★★ ⚠ same condition
ARPC1B p.Arg142Cys Uncertain significance ★★ ⚠ same condition
ARPC1B p.Arg167Trp Uncertain significance ★★ ⚠ same condition
ARPC1B p.Arg216Cys Uncertain significance ★★ ⚠ same condition
ARPC1B p.Asn109Lys Uncertain significance ★★ ⚠ same condition
ARPC1B p.Asn327Ser Uncertain significance ★★ ⚠ 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/arpc1b-p-asp232asn (accessed [today's date]).

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