Is DFFA p.Arg307Gln (c.920G>A) pathogenic?

DFFA p.Arg307Gln (c.920G>A) is classified Uncertain significance in DFFA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.1108); Ultra-rare (popmax 0.0164%, mid).

How common is DFFA p.Arg307Gln (c.920G>A) in the general population?

DFFA p.Arg307Gln (c.920G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about DFFA p.Arg307Gln (c.920G>A)?

AlphaMissense predicts likely benign (score 0.1108) — an in-silico prediction, not a clinical call.

DFFA p.Arg307Gln

c.920G>A · VCV4659663

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1108 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1108	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -5.95	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 2.2	GERP 0.64, phastCons 0.59
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.55 · regional, not allelic
Overall
CADD	23.4	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00285% 46/1,614,062 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.004%	24,975
European (non-Finnish)	0.00322%	31,054
East Asian	0.00223%	44,880
Admixed American	0.00167%	59,988
Remaining individualsnot grpmax-eligible	0.0016%	62,488
Finnishnot grpmax-eligible	0.00156%	64,040

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.Arg307Gln
Coding: c.920G>A
MANE Select: NM_004401
Type: single nucleotide variant
Location: chr1:10461566 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.25 · 3 PDB
Residue 307: the 'disordered' region

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

Similar variants

DFFA p.Arg307Trp Uncertain significance ★ ⚠ same residue
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

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-arg307gln (accessed [today's date]).

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