Is DES p.Ser7Phe (c.20C>T) pathogenic?

DES p.Ser7Phe (c.20C>T) is classified Uncertain significance in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-17). AlphaMissense: ambiguous (0.3402); No allele count reported in gnomAD v4.1 (AN 1,599,238).

How common is DES p.Ser7Phe (c.20C>T) in the general population?

DES p.Ser7Phe (c.20C>T) is no allele count reported in gnomAD v4.1 (AN 1,599,238) (gnomAD).

What do computational predictors say about DES p.Ser7Phe (c.20C>T)?

AlphaMissense predicts ambiguous (score 0.3402) — an in-silico prediction, not a clinical call.

DES p.Ser7Phe

c.20C>T · rs903985237 · VCV594969

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3402 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,599,238)

Computational evidence

Protein change
AlphaMissense	0.3402	ambiguous
REVEL	0.555	indeterminate
SaProt	LLR -9.99	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.58, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic
Overall
CADD	25.2	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

No allele count reported in gnomAD v4.1 (AN 1,599,238). 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.Ser7Phe
Coding: c.20C>T
MANE Select: NM_001927
dbSNP: rs903985237
Type: single nucleotide variant
Location: chr2:219418482 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 7: a modified residue (phosphoserine; by cdk1); the 'head' region; a UniProt-annotated variant site (in mfm1)

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

Similar variants

DES p.Ser7= Likely benign ★ 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
DES c.736-1G>A Likely pathogenic ★★ same type
DES p.Ala120Pro 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/des-p-ser7phe (accessed [today's date]).

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