Is DES p.Ala134Val (c.401C>T) pathogenic?

DES p.Ala134Val (c.401C>T) is classified Uncertain significance in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-26). AlphaMissense: likely benign (0.1716); Absent from gnomAD v4.1.

How common is DES p.Ala134Val (c.401C>T) in the general population?

DES p.Ala134Val (c.401C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DES p.Ala134Val (c.401C>T)?

AlphaMissense predicts likely benign (score 0.1716) — an in-silico prediction, not a clinical call.

DES p.Ala134Val

c.401C>T · VCV4688778

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1716 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,576,344)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1716	likely benign
REVEL	0.443	indeterminate
SaProt	LLR -8.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -3.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic
Overall
CADD	28.4	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

No allele count reported in gnomAD v4.1 (AN 1,576,344). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DES
Protein: p.Ala134Val
Coding: c.401C>T
MANE Select: NM_001927
Type: single nucleotide variant
Location: chr2:219418863 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 134: the if rod domain; the 'coil 1a' region

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

Similar variants

DES p.Ala134Glu Uncertain significance ★ same residue
DES p.Ala134= Likely benign ★ same residue
DES p.Ala134fs Pathogenic/Likely pathogenic ★★ same residue
DES c.1289-2A>G Pathogenic/Likely pathogenic ★★ same type
DES c.579-2A>C Likely pathogenic ★★ same type
DES c.735+1G>A Pathogenic/Likely pathogenic ★★ same type
DES c.735+1G>C Pathogenic/Likely pathogenic ★★ same type
DES c.735+3A>G 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/des-p-ala134val (accessed [today's date]).

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