Is DFFA p.Arg291Gln (c.872G>A) pathogenic?

DFFA p.Arg291Gln (c.872G>A) is classified Likely benign in DFFA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely benign (0.0616); Ultra-rare (popmax 0.0579%, eas).

How common is DFFA p.Arg291Gln (c.872G>A) in the general population?

DFFA p.Arg291Gln (c.872G>A) is ultra-rare (popmax 0.0579%, eas) (gnomAD).

What do computational predictors say about DFFA p.Arg291Gln (c.872G>A)?

AlphaMissense predicts likely benign (score 0.0616) — an in-silico prediction, not a clinical call.

DFFA p.Arg291Gln

c.872G>A · rs372939210 · VCV2462594

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0616 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0579%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0616	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.98	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 -0.51	GERP -3.2
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.55 · regional, not allelic
Overall
CADD	7.801	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 0.0579% East Asian · 26/44,888 alleles

Filtering AF 0.0405% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0347%

Overall 0.00725% 117/1,614,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0579%	1,726
South Asian	0.0263%	3,796
Remaining individualsnot grpmax-eligible	0.024%	4,166
Middle Eastern	0.0164%	6,084
African / African-American	0.00801%	12,492
European (non-Finnish)	0.00356%	28,096
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00333%	30,000

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: DFFA
Protein: p.Arg291Gln
Coding: c.872G>A
MANE Select: NM_004401
dbSNP: rs372939210
Type: single nucleotide variant
Location: chr1:10461614 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.25 · 3 PDB
Residue 291: an α-helix

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

Similar variants

DFFA p.Arg296Cys Likely benign ★★ ⚠ same type
DFFA p.Cys165Arg Benign ★★ same type
DFFA p.Thr300= Benign ★★ same type
DFFA p.Ala236Val Uncertain significance ★ ⚠ same type
DFFA p.Ala250Pro Uncertain significance ★ ⚠ same type
DFFA p.Ala250Ser Uncertain significance ★ ⚠ same type
DFFA p.Ala294Thr Uncertain significance ★ ⚠ same type
DFFA p.Ala51Pro 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/dffa-p-arg291gln (accessed [today's date]).

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