Is DES p.Ser424Phe (c.1271C>T) pathogenic?

DES p.Ser424Phe (c.1271C>T) is classified Uncertain significance in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2016-10-24). AlphaMissense: likely pathogenic (0.6068); Absent from gnomAD v4.1.

How common is DES p.Ser424Phe (c.1271C>T) in the general population?

DES p.Ser424Phe (c.1271C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DES p.Ser424Phe (c.1271C>T)?

AlphaMissense predicts likely pathogenic (score 0.6068) — an in-silico prediction, not a clinical call.

DES p.Ser424Phe

c.1271C>T · rs886042791 · VCV284105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6068 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6068	likely pathogenic
REVEL	0.758	pathogenic-leaning
SaProt	LLR -12.06	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 0.92	unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: DES
Protein: p.Ser424Phe
Coding: c.1271C>T
MANE Select: NM_001927
dbSNP: rs886042791
Type: single nucleotide variant
Location: chr2:219423803 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 424: the 'tail' region; a modified residue (phosphoserine)

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

Similar variants

DES p.Ser424= Likely benign ★★ same residue
DES p.Ser424Ala Uncertain significance ★ ⚠ same residue
DES p.Ser424fs 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-ser424phe (accessed [today's date]).

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