Is ARPC1B p.Asp232Glu (c.696C>G) pathogenic?

ARPC1B p.Asp232Glu (c.696C>G) is classified Likely benign in ARPC1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.0639); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ARPC1B p.Asp232Glu (c.696C>G)?

ARPC1B p.Asp232Glu (c.696C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ARPC1B p.Asp232Glu (c.696C>G) in the general population?

ARPC1B p.Asp232Glu (c.696C>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about ARPC1B p.Asp232Glu (c.696C>G)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

ARPC1B p.Asp232Glu

c.696C>G · VCV4585462

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -6.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.6	GERP -3.7
Regional constraint	o/e 0.89	unconstrained · MANE · 8,771 bp · p 0.0087 · regional, not allelic
Overall
CADD	6.231	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 0.000339% European (non-Finnish) · 4/1,179,702 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000411% 6/1,461,198 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)grpmax	0.000339%	294,925

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp232Glu
Coding: c.696C>G
MANE Select: NM_005720
Type: single nucleotide variant
Location: chr7:99391088 (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.Asp232Asn Conflicting classifications of pathogenicity ★ ⚠ 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-asp232glu (accessed [today's date]).

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