Is DLD p.His247Arg (c.740A>G) pathogenic?

DLD p.His247Arg (c.740A>G) is classified Uncertain significance in DLD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely benign (0.2648); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with DLD p.His247Arg (c.740A>G)?

DLD p.His247Arg (c.740A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DLD p.His247Arg (c.740A>G) in the general population?

DLD p.His247Arg (c.740A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DLD p.His247Arg (c.740A>G)?

AlphaMissense predicts likely benign (score 0.2648) — an in-silico prediction, not a clinical call.

DLD p.His247Arg

c.740A>G · VCV3502263

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2648 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2648	likely benign
REVEL	0.377	indeterminate
SaProt	LLR -6.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 0.88, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 28 kb · p 0.0061 · regional, not allelic
Overall
CADD	23.9	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 0.00446% East Asian · 2/44,818 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000342% 5/1,461,624 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,409
African / African-American	0.00133%	75,026
European (non-Finnish)	0.00017%	589,953

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.His247Arg
Coding: c.740A>G
MANE Select: NM_000108
Type: single nucleotide variant
Location: chr7:107915561 (GRCh38)
Gene constraint: LOEUF 0.727 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.69 · 17 PDB
Residue 247: a β-strand

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.His247= 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-his247arg (accessed [today's date]).

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