Is DLD p.Ala424Gly (c.1271C>G) pathogenic?

DLD p.Ala424Gly (c.1271C>G) is classified Uncertain significance in DLD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-16). AlphaMissense: likely benign (0.2141); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DLD p.Ala424Gly (c.1271C>G)?

DLD p.Ala424Gly (c.1271C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DLD p.Ala424Gly (c.1271C>G) in the general population?

DLD p.Ala424Gly (c.1271C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLD p.Ala424Gly (c.1271C>G)?

AlphaMissense predicts likely benign (score 0.2141) — an in-silico prediction, not a clinical call.

DLD p.Ala424Gly

c.1271C>G · VCV3272211

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2141 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2141	likely benign
REVEL	0.686	pathogenic-leaning
SaProt	LLR -9.49	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 28 kb · p 0.0061 · 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: DLD
Protein: p.Ala424Gly
Coding: c.1271C>G
MANE Select: NM_000108
Type: single nucleotide variant
Location: chr7:107917958 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB
Residue 424: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLD p.Ala424= Likely benign ★ same residue
DLD p.Ala501Val Uncertain significance ★★ ⚠ same condition
DLD p.Gly154Glu Uncertain significance ★★ ⚠ same condition
DLD p.Gly287Glu Uncertain significance ★★ ⚠ same condition
DLD p.Lys410Gln Uncertain significance ★★ ⚠ same condition
DLD p.Met255Thr Uncertain significance ★★ ⚠ same condition
DLD p.Thr157Ser Uncertain significance ★★ ⚠ same condition
DLD p.Thr171Pro Uncertain significance ★★ ⚠ same condition

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/dld-p-ala424gly (accessed [today's date]).

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