Is DUXA p.Gly71Arg (c.211G>A) pathogenic?

DUXA p.Gly71Arg (c.211G>A) is classified Likely benign in DUXA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-31). AlphaMissense: likely benign (0.117); Ultra-rare (popmax 0.0227%, nfe).

How common is DUXA p.Gly71Arg (c.211G>A) in the general population?

DUXA p.Gly71Arg (c.211G>A) is ultra-rare (popmax 0.0227%, nfe) (gnomAD).

What do computational predictors say about DUXA p.Gly71Arg (c.211G>A)?

AlphaMissense predicts likely benign (score 0.117) — an in-silico prediction, not a clinical call.

DUXA p.Gly71Arg

c.211G>A · rs200454436 · VCV2521196

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.117 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.117	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -1.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4
Regional constraint	o/e 1.02	unconstrained · MANE · 13 kb · p 0.79 · regional, not allelic
Overall
CADD	0.083	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 0.0227% European (non-Finnish) · 268/1,180,006 alleles

Filtering AF 0.0204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0195%

Overall 0.0176% 284/1,613,908 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0227%	4,403
Remaining individualsnot grpmax-eligible	0.016%	6,248
East Asian	0.00891%	11,223
African / African-American	0.00267%	37,451

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: DUXA
Protein: p.Gly71Arg
Coding: c.211G>A
MANE Select: NM_001012729
dbSNP: rs200454436
Type: single nucleotide variant
Location: chr19:57159248 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.04
Residue 71: a DNA-binding region

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

Similar variants

DUXA p.Ala166Val Uncertain significance ★ ⚠ same type
DUXA p.Ala68Pro Uncertain significance ★ ⚠ same type
DUXA p.Arg103Gln Uncertain significance ★ ⚠ same type
DUXA p.Arg103Trp Uncertain significance ★ ⚠ same type
DUXA p.Arg105Cys Uncertain significance ★ ⚠ same type
DUXA p.Arg16Thr Uncertain significance ★ ⚠ same type
DUXA p.Arg17Cys Uncertain significance ★ ⚠ same type
DUXA p.Arg19His 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/duxa-p-gly71arg (accessed [today's date]).

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