Is ARPC1B p.Ala261= (c.783G>A) pathogenic?

ARPC1B p.Ala261= (c.783G>A) is classified Pathogenic in ARPC1B (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-07-05). Very rare (popmax 0.00167%, amr); Associated with platelet abnormalities with eosinophilia and immune-mediated inflammatory disease.

How common is ARPC1B p.Ala261= (c.783G>A) in the general population?

ARPC1B p.Ala261= (c.783G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

ARPC1B p.Ala261=

Q: What condition is associated with ARPC1B p.Ala261= (c.783G>A)?

ARPC1B p.Ala261= (c.783G>A) is associated with platelet abnormalities with eosinophilia and immune-mediated inflammatory disease (ClinVar).

c.783G>A · rs779597975 · VCV1030961

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

platelet abnormalities with eosinophilia and immune-mediated inflammatory disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.83	donor loss · deltas
Pangolin	Δ0.66	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.9	GERP -0.85, phastCons 1
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,964 alleles

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

Overall 0.000434% 7/1,613,716 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,240
Admixed Americangrpmax	0.00167%	59,964
European (non-Finnish)	0.000339%	294,989

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.Ala261=
Coding: c.783G>A
MANE Select: NM_005720
dbSNP: rs779597975
Type: single nucleotide variant
Location: chr7:99391253 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 4 PDB
Residue 261: a β-strand

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

Disease context

platelet abnormalities with eosinophilia and immune-mediated inflammatory disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARPC1B p.Ala261Val Uncertain significance ★★ ⚠ same residue
ARPC1B p.Ala261Ser Uncertain significance ★ ⚠ same residue
ARPC1B c.64+2T>A Pathogenic ★★ same condition
ARPC1B p.Ala238Val Uncertain significance ★★ ⚠ same condition
ARPC1B p.Arg103His Uncertain significance ★★ ⚠ same condition
ARPC1B p.Cys162Gly Uncertain significance ★★ ⚠ same condition
ARPC1B p.Gly39Ser Uncertain significance ★★ ⚠ same condition
ARPC1B p.Met350Arg 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-ala261 (accessed [today's date]).

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