Is ARPC2 p.Arg300His (c.899G>A) pathogenic?

ARPC2 p.Arg300His (c.899G>A) is classified Uncertain significance in ARPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: ambiguous (0.4536); Very rare (popmax 0.00167%, amr).

How common is ARPC2 p.Arg300His (c.899G>A) in the general population?

ARPC2 p.Arg300His (c.899G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about ARPC2 p.Arg300His (c.899G>A)?

AlphaMissense predicts ambiguous (score 0.4536) — an in-silico prediction, not a clinical call.

ARPC2 p.Arg300His

c.899G>A · VCV3948565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4536 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4536	ambiguous
REVEL	0.279	benign-leaning
SaProt	LLR -11.01	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 8,470 bp · p 1e-06 · regional, not allelic
Overall
CADD	29.9	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 0.00167% Admixed American · 1/59,956 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000342% 5/1,461,692 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,956
South Asian	0.0011%	91,050
European (non-Finnish)	0.000254%	393,315

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: ARPC2
Protein: p.Arg300His
Coding: c.899G>A
MANE Select: NM_152862
Type: single nucleotide variant
Location: chr2:218253911 (GRCh38)
Gene constraint: LOEUF 0.319 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.03 · 5 PDB

Full ARPC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARPC2 c.677-3C>T Benign ★★ same type
ARPC2 p.Leu3= Benign ★★ same type
ARPC2 p.Ala69Val Uncertain significance ★ ⚠ same type
ARPC2 p.Arg237Gln Uncertain significance ★ ⚠ same type
ARPC2 p.Arg267Trp Uncertain significance ★ ⚠ same type
ARPC2 p.Arg281Cys Uncertain significance ★ ⚠ same type
ARPC2 p.Arg281His Uncertain significance ★ ⚠ same type
ARPC2 p.Asn219Asp 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/arpc2-p-arg300his (accessed [today's date]).

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