Is ARPC1B p.Asp149Tyr (c.445G>T) pathogenic?

ARPC1B p.Asp149Tyr (c.445G>T) is classified Conflicting classifications of pathogenicity in ARPC1B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-01). AlphaMissense: likely pathogenic (0.9662); Ultra-rare (popmax 0.0383%, nfe).

How common is ARPC1B p.Asp149Tyr (c.445G>T) in the general population?

ARPC1B p.Asp149Tyr (c.445G>T) is ultra-rare (popmax 0.0383%, nfe) (gnomAD).

What do computational predictors say about ARPC1B p.Asp149Tyr (c.445G>T)?

AlphaMissense predicts likely pathogenic (score 0.9662) — an in-silico prediction, not a clinical call.

ARPC1B p.Asp149Tyr

c.445G>T · rs143427534 · VCV731661

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9662 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9662	likely pathogenic
REVEL	0.694	pathogenic-leaning
SaProt	LLR -13.18	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 8,771 bp · p 0.0087 · regional, not allelic
Overall
CADD	33.0	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 0.0383% European (non-Finnish) · 452/1,180,034 alleles

Filtering AF 0.0353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0342%

Overall 0.0589% 950/1,614,036 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.36%	74
Remaining individualsnot grpmax-eligible	0.136%	735
European (non-Finnish)grpmax	0.0383%	2,611
African / African-American	0.0107%	9,366
Admixed American	0.005%	19,995

Ashkenazi Jewish 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.Asp149Tyr
Coding: c.445G>T
MANE Select: NM_005720
dbSNP: rs143427534
Type: single nucleotide variant
Location: chr7:99389957 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 4 PDB
Residue 149: a β-strand

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

Similar variants

ARPC1B p.Asp149Ala 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
ARPC1B p.Ala238Val 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-asp149tyr (accessed [today's date]).

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