Is ARGFX p.Arg82His (c.245G>A) pathogenic?

ARGFX p.Arg82His (c.245G>A) is classified Uncertain significance in ARGFX (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: ambiguous (0.4471); Ultra-rare (popmax 0.0433%, amr).

How common is ARGFX p.Arg82His (c.245G>A) in the general population?

ARGFX p.Arg82His (c.245G>A) is ultra-rare (popmax 0.0433%, amr) (gnomAD).

What do computational predictors say about ARGFX p.Arg82His (c.245G>A)?

AlphaMissense predicts ambiguous (score 0.4471) — an in-silico prediction, not a clinical call.

ARGFX p.Arg82His

c.245G>A · rs531332897 · VCV2371680

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4471 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0433%, amr)

Computational evidence

Protein change
AlphaMissense	0.4471	ambiguous
REVEL	0.384	indeterminate
SaProt	LLR -7.34	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.53	GERP 0.67
Regional constraint	o/e 0.87	unconstrained · MANE · 16 kb · p 0.019 · regional, not allelic
Overall
CADD	15.89	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 0.0433% Admixed American · 26/59,980 alleles

Filtering AF 0.0353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0341%

Overall 0.0304% 491/1,613,368 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0433%	2,307
European (non-Finnish)	0.0382%	2,616
Remaining individualsnot grpmax-eligible	0.0112%	8,918
African / African-American	0.00401%	24,961
East Asian	0.00223%	44,882
South Asian	0.0022%	45,500
Finnishnot grpmax-eligible	0.00156%	64,030

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: ARGFX
Protein: p.Arg82His
Coding: c.245G>A
MANE Select: NM_001012659
dbSNP: rs531332897
Type: single nucleotide variant
Location: chr3:121584941 (GRCh38)
Gene constraint: LOEUF 1.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.78
Residue 82: a DNA-binding region

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

Similar variants

ARGFX p.Ala190Glu Uncertain significance ★ ⚠ same type
ARGFX p.Arg114Thr Uncertain significance ★ ⚠ same type
ARGFX p.Arg129Gln Uncertain significance ★ ⚠ same type
ARGFX p.Arg129Trp Uncertain significance ★ ⚠ same type
ARGFX p.Arg130Gln Uncertain significance ★ ⚠ same type
ARGFX p.Arg212Met Uncertain significance ★ ⚠ same type
ARGFX p.Asn188Ile Uncertain significance ★ ⚠ same type
ARGFX p.Asp238Tyr 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/argfx-p-arg82his (accessed [today's date]).

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