Is ARG2 p.Arg4Trp (c.10A>T) pathogenic?

ARG2 p.Arg4Trp (c.10A>T) is classified Likely benign in ARG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-04). AlphaMissense: likely benign (0.2036); Rare (popmax 0.222%, amr).

How common is ARG2 p.Arg4Trp (c.10A>T) in the general population?

ARG2 p.Arg4Trp (c.10A>T) is rare (popmax 0.222%, amr) (gnomAD).

What do computational predictors say about ARG2 p.Arg4Trp (c.10A>T)?

AlphaMissense predicts likely benign (score 0.2036) — an in-silico prediction, not a clinical call.

ARG2 p.Arg4Trp

c.10A>T · rs143988405 · VCV717631

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2036 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.222%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2036	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -8.90	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.37	GERP -5.1, phastCons 0.002
Regional constraint	o/e 0.89	unconstrained · MANE · 31 kb · p 0.02 · regional, not allelic
Overall
CADD	17.57	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 0.222% Admixed American · 130/58,498 alleles

Filtering AF 0.191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.179%

Overall 0.0293% 470/1,602,552 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.222%	450
Middle Eastern	0.149%	669
Remaining individualsnot grpmax-eligible	0.0483%	2,068
African / African-American	0.0324%	3,086
European (non-Finnish)	0.0233%	4,288
East Asian	0.00458%	21,820
Ashkenazi Jewishnot grpmax-eligible	0.00343%	29,172

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: ARG2
Protein: p.Arg4Trp
Coding: c.10A>T
MANE Select: NM_001172
dbSNP: rs143988405
Type: single nucleotide variant
Location: chr14:67619987 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.55 · 18 PDB

Full ARG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARG2 p.Ala308= Benign/Likely benign ★★ same type
ARG2 p.Gly36= Benign ★★ same type
ARG2 p.Ala106Pro Uncertain significance ★ ⚠ same type
ARG2 p.Ala123Thr Uncertain significance ★ ⚠ same type
ARG2 p.Ala191Ser Uncertain significance ★ ⚠ same type
ARG2 p.Ala31Asp Uncertain significance ★ ⚠ same type
ARG2 p.Arg105Ser Uncertain significance ★ ⚠ same type
ARG2 p.Arg132Gln 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/arg2-p-arg4trp (accessed [today's date]).

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