Is DLD p.Cys9Ser (c.25T>A) pathogenic?

DLD p.Cys9Ser (c.25T>A) is classified Uncertain significance in DLD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: likely benign (0.1135); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DLD p.Cys9Ser (c.25T>A)?

DLD p.Cys9Ser (c.25T>A) is associated with Inborn genetic diseases (ClinVar).

How common is DLD p.Cys9Ser (c.25T>A) in the general population?

DLD p.Cys9Ser (c.25T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLD p.Cys9Ser (c.25T>A)?

AlphaMissense predicts likely benign (score 0.1135) — an in-silico prediction, not a clinical call.

DLD p.Cys9Ser

c.25T>A · rs2535557737 · VCV3082700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1135 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1135	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -4.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.26	GERP 2.1, phastCons 0.34
Regional constraint	o/e 0.89	unconstrained · MANE · 28 kb · p 0.0061 · regional, not allelic
Overall
CADD	16.78	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

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.Cys9Ser
Coding: c.25T>A
MANE Select: NM_000108
dbSNP: rs2535557737
Type: single nucleotide variant
Location: chr7:107891275 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DLD p.Cys9= Likely benign ★ same residue
DLD p.Ala501Val Uncertain significance ★★ ⚠ same condition
DLD p.Gly154Glu Uncertain significance ★★ ⚠ same condition
DLD p.Gly287Glu Uncertain significance ★★ ⚠ same condition
DLD p.Lys410Gln Uncertain significance ★★ ⚠ same condition
DLD p.Met255Thr Uncertain significance ★★ ⚠ same condition
DLD p.Thr157Ser Uncertain significance ★★ ⚠ same condition
DLD p.Thr171Pro Uncertain significance ★★ ⚠ same condition

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-cys9ser (accessed [today's date]).

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