Is ARGFX p.Arg129Gln (c.386G>A) pathogenic?

ARGFX p.Arg129Gln (c.386G>A) is classified Uncertain significance in ARGFX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely benign (0.209); Ultra-rare (popmax 0.0118%, sas).

How common is ARGFX p.Arg129Gln (c.386G>A) in the general population?

ARGFX p.Arg129Gln (c.386G>A) is ultra-rare (popmax 0.0118%, sas) (gnomAD).

What do computational predictors say about ARGFX p.Arg129Gln (c.386G>A)?

AlphaMissense predicts likely benign (score 0.209) — an in-silico prediction, not a clinical call.

ARGFX p.Arg129Gln

c.386G>A · VCV4642071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.209 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.209	likely benign
REVEL	0.421	indeterminate
SaProt	LLR -8.05	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 -1.2	GERP -0.95
Regional constraint	o/e 0.87	unconstrained · MANE · 16 kb · p 0.019 · regional, not allelic
Overall
CADD	16.14	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0118% South Asian · 10/84,390 alleles

Filtering AF 0.00638% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00485%

Overall 0.00209% 33/1,578,684 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0118%	8,439
Admixed American	0.00727%	13,747
Remaining individualsnot grpmax-eligible	0.00164%	60,988
European (non-Finnish)	0.00155%	64,636

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.Arg129Gln
Coding: c.386G>A
MANE Select: NM_001012659
Type: single nucleotide variant
Location: chr3:121586038 (GRCh38)
Gene constraint: LOEUF 1.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.78
Residue 129: a DNA-binding region

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

Similar variants

ARGFX p.Arg129Trp Uncertain significance ★ ⚠ same residue
ARGFX p.Ala190Glu Uncertain significance ★ ⚠ same type
ARGFX p.Arg114Thr Uncertain significance ★ ⚠ same type
ARGFX p.Arg130Gln 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-arg129gln (accessed [today's date]).

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