Is ARPC1B p.Arg167Trp (c.499C>T) pathogenic?

ARPC1B p.Arg167Trp (c.499C>T) is classified Uncertain significance in ARPC1B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-23). AlphaMissense: likely pathogenic (0.946); Ultra-rare (popmax 0.0483%, amr); Associated with Inborn genetic diseases.

What condition is associated with ARPC1B p.Arg167Trp (c.499C>T)?

ARPC1B p.Arg167Trp (c.499C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARPC1B p.Arg167Trp (c.499C>T) in the general population?

ARPC1B p.Arg167Trp (c.499C>T) is ultra-rare (popmax 0.0483%, amr) (gnomAD).

What do computational predictors say about ARPC1B p.Arg167Trp (c.499C>T)?

AlphaMissense predicts likely pathogenic (score 0.946) — an in-silico prediction, not a clinical call.

ARPC1B p.Arg167Trp

c.499C>T · rs190333133 · VCV1368889

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.946 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0483%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.946	likely pathogenic
REVEL	0.679	pathogenic-leaning
SaProt	LLR -12.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.64 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.41	GERP -1.8, phastCons 0.96
Regional constraint	o/e 0.89	unconstrained · MANE · 8,771 bp · p 0.0087 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0483% Admixed American · 29/60,014 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0299%

Overall 0.00731% 118/1,613,610 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0483%	2,069
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0144%	6,944
Finnishnot grpmax-eligible	0.00784%	12,762
European (non-Finnish)	0.00593%	16,853
East Asian	0.00446%	22,441
African / African-American	0.00133%	75,046
South Asian	0.0011%	91,072

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.Arg167Trp
Coding: c.499C>T
MANE Select: NM_005720
dbSNP: rs190333133
Type: single nucleotide variant
Location: chr7:99390011 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 4 PDB
Residue 167: a β-strand

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

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ARPC1B p.Arg142Cys 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
ARPC1B p.Asp149Ala Uncertain significance ★★ ⚠ same condition
ARPC1B p.Glu108Lys 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-arg167trp (accessed [today's date]).

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