Is ARPC1B p.Asn327Ser (c.980A>G) pathogenic?

ARPC1B p.Asn327Ser (c.980A>G) is classified Uncertain significance in ARPC1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-05). AlphaMissense: likely pathogenic (0.9046); Ultra-rare (popmax 0.0236%, amr); Associated with Inborn genetic diseases.

What condition is associated with ARPC1B p.Asn327Ser (c.980A>G)?

ARPC1B p.Asn327Ser (c.980A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ARPC1B p.Asn327Ser (c.980A>G) in the general population?

ARPC1B p.Asn327Ser (c.980A>G) is ultra-rare (popmax 0.0236%, amr) (gnomAD).

What do computational predictors say about ARPC1B p.Asn327Ser (c.980A>G)?

AlphaMissense predicts likely pathogenic (score 0.9046) — an in-silico prediction, not a clinical call.

ARPC1B p.Asn327Ser

c.980A>G · rs903910250 · VCV1412865

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9046 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0236%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9046	likely pathogenic
REVEL	0.439	indeterminate
SaProt	LLR -11.33	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 8,771 bp · p 0.0087 · regional, not allelic
Overall
CADD	24.8	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 0.0236% Admixed American · 12/50,760 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00168% 26/1,544,892 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0236%	4,230
Remaining individualsnot grpmax-eligible	0.00502%	19,907
African / African-American	0.00137%	72,866
European (non-Finnish)	0.000875%	114,328

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.Asn327Ser
Coding: c.980A>G
MANE Select: NM_005720
dbSNP: rs903910250
Type: single nucleotide variant
Location: chr7:99392867 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.81 · 4 PDB

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.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.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-asn327ser (accessed [today's date]).

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