Is DLD p.Tyr8Phe (c.23A>T) pathogenic?

DLD p.Tyr8Phe (c.23A>T) is classified Uncertain significance in DLD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-18). AlphaMissense: likely benign (0.0721); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DLD p.Tyr8Phe (c.23A>T)?

DLD p.Tyr8Phe (c.23A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DLD p.Tyr8Phe (c.23A>T) in the general population?

DLD p.Tyr8Phe (c.23A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DLD p.Tyr8Phe (c.23A>T)?

AlphaMissense predicts likely benign (score 0.0721) — an in-silico prediction, not a clinical call.

DLD p.Tyr8Phe

c.23A>T · rs756418833 · VCV2359320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0721 · 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	0.0721	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -4.62	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 0.43	GERP 0.88, phastCons 0.26
Regional constraint	o/e 0.89	unconstrained · MANE · 28 kb · p 0.0061 · regional, not allelic
Overall
CADD	16.87	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.Tyr8Phe
Coding: c.23A>T
MANE Select: NM_000108
dbSNP: rs756418833
Type: single nucleotide variant
Location: chr7:107891273 (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.Tyr8Ter Pathogenic ★ same residue
DLD p.Tyr8= 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

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-tyr8phe (accessed [today's date]).

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