Is ARPC5 p.Ser2Trp (c.5C>G) pathogenic?

ARPC5 p.Ser2Trp (c.5C>G) is classified Uncertain significance in ARPC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely pathogenic (0.9412); Very rare (popmax 0.00178%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ARPC5 p.Ser2Trp (c.5C>G)?

ARPC5 p.Ser2Trp (c.5C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ARPC5 p.Ser2Trp (c.5C>G) in the general population?

ARPC5 p.Ser2Trp (c.5C>G) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about ARPC5 p.Ser2Trp (c.5C>G)?

AlphaMissense predicts likely pathogenic (score 0.9412) — an in-silico prediction, not a clinical call.

ARPC5 p.Ser2Trp

c.5C>G · rs370723137 · VCV3129805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9412 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9412	likely pathogenic
REVEL	0.332	indeterminate
SaProt	LLR -13.00	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 8.5	GERP 2.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 36 bp · p 0.59 · regional, not allelic
Overall
CADD	25.9	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 0.00178% European (non-Finnish) · 21/1,179,002 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0013% 21/1,611,626 alleles · very rare

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: ARPC5
Protein: p.Ser2Trp
Coding: c.5C>G
MANE Select: NM_005717
dbSNP: rs370723137
Type: single nucleotide variant
Location: chr1:183635655 (GRCh38)
Gene constraint: LOEUF 0.725 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 92.42 · 2 PDB
Residue 2: a modified residue (n-acetylserine)

Full ARPC5 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

ARPC5 p.Ala54Thr Uncertain significance ★ ⚠ same condition
ARPC5 p.Arg47Leu Uncertain significance ★ ⚠ same condition
ARPC5 p.Asn101Ser Uncertain significance ★ ⚠ same condition
ARPC5 p.Asn61Ser Uncertain significance ★ ⚠ same condition
ARPC5 p.Asp104Gly Uncertain significance ★ ⚠ same condition
ARPC5 p.Asp32Glu Uncertain significance ★ ⚠ same condition
ARPC5 p.Ile78Val Uncertain significance ★ ⚠ same condition
ARPC5 p.Ile84Leu 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/arpc5-p-ser2trp (accessed [today's date]).

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