Is DLD p.Val248Ile (c.742G>A) pathogenic?

DLD p.Val248Ile (c.742G>A) is classified Uncertain significance in DLD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-26). AlphaMissense: likely benign (0.1133); Very rare (popmax 0.00666%, afr).

How common is DLD p.Val248Ile (c.742G>A) in the general population?

DLD p.Val248Ile (c.742G>A) is very rare (popmax 0.00666%, afr) (gnomAD).

What do computational predictors say about DLD p.Val248Ile (c.742G>A)?

AlphaMissense predicts likely benign (score 0.1133) — an in-silico prediction, not a clinical call.

DLD p.Val248Ile

c.742G>A · VCV3379787

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1133 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1133	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -5.91	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 6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 28 kb · p 0.0061 · regional, not allelic
Overall
CADD	17.11	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

Grpmax group 0.00666% African / African-American · 5/75,028 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000558% 9/1,613,890 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00666%	15,006
Remaining individualsnot grpmax-eligible	0.0032%	31,246
Admixed American	0.00167%	60,008
European (non-Finnish)	8.48e-05%	1,179,889

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DLD
Protein: p.Val248Ile
Coding: c.742G>A
MANE Select: NM_000108
Type: single nucleotide variant
Location: chr7:107915563 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB
Residue 248: a β-strand

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

Similar variants

DLD p.Val248= Likely benign ★ same residue
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

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-val248ile (accessed [today's date]).

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