Is ARPC1B p.Thr80= (c.240G>A) pathogenic?

ARPC1B p.Thr80= (c.240G>A) is classified Likely benign in ARPC1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-29). Ultra-rare (popmax 0.0165%, sas).

How common is ARPC1B p.Thr80= (c.240G>A) in the general population?

ARPC1B p.Thr80= (c.240G>A) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

ARPC1B p.Thr80=

c.240G>A · rs373569413 · VCV1567040

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.8	GERP -3.7
Overall
CADD	2.253	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/91,082 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.0115% 186/1,614,130 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,072
European (non-Finnish)	0.0138%	7,239
African / African-American	0.00533%	18,759
Remaining individualsnot grpmax-eligible	0.0048%	20,835
East Asian	0.00223%	44,878

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.Thr80=
Coding: c.240G>A
MANE Select: NM_005720
dbSNP: rs373569413
Type: single nucleotide variant
Location: chr7:99388109 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 4 PDB
Residue 80: a β-strand

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

Similar variants

ARPC1B p.Thr80Lys Uncertain significance ★ ⚠ same residue
ARPC1B p.Thr80Met Uncertain significance ★ ⚠ same residue
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

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-thr80 (accessed [today's date]).

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