Is DES p.Ala306Val (c.917C>T) pathogenic?

DES p.Ala306Val (c.917C>T) is classified Uncertain significance in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely benign (0.2841); Very rare (popmax 0.0011%, sas).

How common is DES p.Ala306Val (c.917C>T) in the general population?

DES p.Ala306Val (c.917C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DES p.Ala306Val (c.917C>T)?

AlphaMissense predicts likely benign (score 0.2841) — an in-silico prediction, not a clinical call.

DES p.Ala306Val

c.917C>T · VCV4071709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2841 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2841	likely benign
REVEL	0.838	moderately pathogenic-leaning
SaProt	LLR -7.29	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.71, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic
Overall
CADD	32.0	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 0.0011% South Asian · 1/91,074 alleles

Overall 0.000137% 2/1,461,558 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,074
European (non-Finnish)	8.47e-05%	1,179,980

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: DES
Protein: p.Ala306Val
Coding: c.917C>T
MANE Select: NM_001927
Type: single nucleotide variant
Location: chr2:219420847 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 306: the 'coil 2b' region; the if rod domain; the 'interaction with neb' region

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

Similar variants

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
DES c.736-1G>A Likely pathogenic ★★ same type
DES p.Ala120Pro Pathogenic/Likely pathogenic ★★ same type
DES p.Ala285Val 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/des-p-ala306val (accessed [today's date]).

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