Is DPH1 p.Val28Met (c.82G>A) pathogenic?

DPH1 p.Val28Met (c.82G>A) is classified Uncertain significance in DPH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: likely benign (0.097); Very rare (popmax 0.00891%, eas); Associated with Inborn genetic diseases.

What condition is associated with DPH1 p.Val28Met (c.82G>A)?

DPH1 p.Val28Met (c.82G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DPH1 p.Val28Met (c.82G>A) in the general population?

DPH1 p.Val28Met (c.82G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about DPH1 p.Val28Met (c.82G>A)?

AlphaMissense predicts likely benign (score 0.097) — an in-silico prediction, not a clinical call.

DPH1 p.Val28Met

c.82G>A · rs769439688 · VCV2398935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.097 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.097	likely benign
REVEL	0.039	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -4.3
Regional constraint	o/e 1.07	unconstrained · MANE · 12 kb · p 0.074 · regional, not allelic
Overall
CADD	11.78	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V33M vs ClinVar V28M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,890 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00294%

Overall 0.00397% 64/1,614,028 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,223
Admixed American	0.005%	20,002
South Asian	0.00439%	22,773
European (non-Finnish)	0.00424%	23,601
Remaining individualsnot grpmax-eligible	0.0032%	31,242
Finnishnot grpmax-eligible	0.00156%	63,972

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: DPH1
Protein: p.Val28Met
Coding: c.82G>A
MANE Select: NM_001383
dbSNP: rs769439688
Type: single nucleotide variant
Location: chr17:2033525 (GRCh38)
Gene constraint: LOEUF 1.321 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.00
Residue 28: the 'disordered' region

Full DPH1 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

OVCA2 p.Ala28Pro Uncertain significance ★ ⚠ same residue
OVCA2 p.Ala28Ser Uncertain significance ★ ⚠ same residue
DPH1 p.Arg144Trp Uncertain significance ★★ ⚠ same condition
DPH1 p.Ile241Phe Uncertain significance ★★ same condition
DPH1 p.Lys38Thr Likely benign ★★ same condition
DPH1 c.279-5C>T Uncertain significance ★ same condition
DPH1 c.558+4G>C Uncertain significance ★ same condition
DPH1 c.-12C>T 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/dph1-p-val28met (accessed [today's date]).

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