Is ARGFX p.Arg130Gln (c.389G>A) pathogenic?

ARGFX p.Arg130Gln (c.389G>A) is classified Uncertain significance in ARGFX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: ambiguous (0.4227); Very rare (popmax 0.00271%, afr).

How common is ARGFX p.Arg130Gln (c.389G>A) in the general population?

ARGFX p.Arg130Gln (c.389G>A) is very rare (popmax 0.00271%, afr) (gnomAD).

What do computational predictors say about ARGFX p.Arg130Gln (c.389G>A)?

AlphaMissense predicts ambiguous (score 0.4227) — an in-silico prediction, not a clinical call.

ARGFX p.Arg130Gln

c.389G>A · rs752404821 · VCV2548515

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4227 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, afr)

Computational evidence

Protein change
AlphaMissense	0.4227	ambiguous
REVEL	0.448	indeterminate
SaProt	LLR -9.19	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP -0.86
Regional constraint	o/e 0.87	unconstrained · MANE · 16 kb · p 0.019 · regional, not allelic
Overall
CADD	16.29	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 0.00271% African / African-American · 2/73,750 alleles

Filtering AF 0.00045% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000168%

Overall 0.000506% 8/1,581,692 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00271%	36,875
South Asian	0.00235%	42,579
Finnishnot grpmax-eligible	0.00159%	62,788
European (non-Finnish)	0.000257%	388,365

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.Arg130Gln
Coding: c.389G>A
MANE Select: NM_001012659
dbSNP: rs752404821
Type: single nucleotide variant
Location: chr3:121586041 (GRCh38)
Gene constraint: LOEUF 1.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.78
Residue 130: 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.Arg212Met Uncertain significance ★ ⚠ same type
ARGFX p.Arg82His 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-arg130gln (accessed [today's date]).

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