Is DDN p.Lys271Gln (c.811A>C) pathogenic?

DDN p.Lys271Gln (c.811A>C) is classified Uncertain significance in DDN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-09). AlphaMissense: ambiguous (0.4811); Absent from gnomAD v4.1.

How common is DDN p.Lys271Gln (c.811A>C) in the general population?

DDN p.Lys271Gln (c.811A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDN p.Lys271Gln (c.811A>C)?

AlphaMissense predicts ambiguous (score 0.4811) — an in-silico prediction, not a clinical call.

DDN p.Lys271Gln

c.811A>C · VCV3500302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4811 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4811	ambiguous
REVEL	0.135	moderately benign-leaning
SaProt	LLR -6.03	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 2,544 bp · p 0.18 · regional, not allelic
Overall
CADD	25.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DDN
Protein: p.Lys271Gln
Coding: c.811A>C
MANE Select: NM_015086
Type: single nucleotide variant
Location: chr12:48998065 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 46.28
Residue 271: the 'disordered' region

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

Similar variants

DDN p.Glu661Gly Benign ★★ same type
DDN p.Pro358Arg Benign ★★ same type
DDN p.Ala154Thr Uncertain significance ★ ⚠ same type
DDN p.Ala169Val Uncertain significance ★ ⚠ same type
DDN p.Ala174Glu Uncertain significance ★ ⚠ same type
DDN p.Ala179Thr Uncertain significance ★ ⚠ same type
DDN p.Ala305Thr Uncertain significance ★ ⚠ same type
DDN p.Ala341Thr 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/ddn-p-lys271gln (accessed [today's date]).

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