Is DLD p.Ser88Phe (c.263C>T) pathogenic?

DLD p.Ser88Phe (c.263C>T) is classified Uncertain significance in DLD (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-28). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1.

How common is DLD p.Ser88Phe (c.263C>T) in the general population?

DLD p.Ser88Phe (c.263C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLD p.Ser88Phe (c.263C>T)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

DLD p.Ser88Phe

c.263C>T · rs985832127 · VCV1311933

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic · top 1% in DLD
REVEL	0.518	indeterminate
SaProt	LLR -14.09	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 28 kb · p 0.0061 · regional, not allelic
Overall
CADD	32.0	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: DLD
Protein: p.Ser88Phe
Coding: c.263C>T
MANE Select: NM_000108
dbSNP: rs985832127
Type: single nucleotide variant
Location: chr7:107902389 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB
Residue 88: an α-helix

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

Similar variants

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
DLD p.Arg315Ter 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-ser88phe (accessed [today's date]).

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