Is DFFA p.Lys201Gln (c.601A>C) pathogenic?

DFFA p.Lys201Gln (c.601A>C) is classified Uncertain significance in DFFA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). AlphaMissense: likely benign (0.1487); Very rare (popmax 0.00167%, amr).

How common is DFFA p.Lys201Gln (c.601A>C) in the general population?

DFFA p.Lys201Gln (c.601A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DFFA p.Lys201Gln (c.601A>C)?

AlphaMissense predicts likely benign (score 0.1487) — an in-silico prediction, not a clinical call.

DFFA p.Lys201Gln

c.601A>C · VCV4011042

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1487 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1487	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -5.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.65 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.55 · regional, not allelic
Overall
CADD	23.0	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 0.00167% Admixed American · 1/59,928 alleles

Overall 0.000124% 2/1,613,694 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,928
European (non-Finnish)	8.47e-05%	1,179,952

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.Lys201Gln
Coding: c.601A>C
MANE Select: NM_004401
Type: single nucleotide variant
Location: chr1:10463461 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.25 · 3 PDB

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-lys201gln (accessed [today's date]).

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