Is DLD p.Ala61Val (c.182C>T) pathogenic?

DLD p.Ala61Val (c.182C>T) is classified Likely pathogenic in DLD (ClinVar, Single submitter, 1 submitter; last evaluated 2014-01-18). AlphaMissense: likely pathogenic (0.868); Very rare (popmax 0.00017%, nfe).

How common is DLD p.Ala61Val (c.182C>T) in the general population?

DLD p.Ala61Val (c.182C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about DLD p.Ala61Val (c.182C>T)?

AlphaMissense predicts likely pathogenic (score 0.868) — an in-silico prediction, not a clinical call.

DLD p.Ala61Val

c.182C>T · rs796051947 · VCV203674

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.868 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.868	likely pathogenic ✓ concordant with ClinVar
REVEL	0.663	pathogenic-leaning
SaProt	LLR -14.85	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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 0.89	unconstrained · MANE · 28 kb · p 0.0061 · regional, not allelic
Overall
CADD	30.0	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 0.00017% European (non-Finnish) · 2/1,179,382 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,092 alleles · very rare

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: DLD
Protein: p.Ala61Val
Coding: c.182C>T
MANE Select: NM_000108
dbSNP: rs796051947
Type: single nucleotide variant
Location: chr7:107901801 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB
Residue 61: an α-helix

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

Similar variants

DLD p.Ala61= Likely benign ★ same residue
DLD c.1464+1G>A Pathogenic/Likely pathogenic ★★ same type
DLD c.198+1G>T Likely pathogenic ★★ same type
DLD c.39+1G>A Likely pathogenic ★★ same type
DLD c.40-2A>G Likely pathogenic ★★ same type
DLD c.583-1G>C Likely pathogenic ★★ same type
DLD c.684+1G>T Likely pathogenic ★★ same type
DLD c.875+1G>A Pathogenic/Likely pathogenic ★★ 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/dld-p-ala61val (accessed [today's date]).

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