Is DPH7 p.Val56Asp (c.167T>A) pathogenic?

DPH7 p.Val56Asp (c.167T>A) is classified Uncertain significance in DPH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.0843); Ultra-rare (popmax 0.01%, amr).

How common is DPH7 p.Val56Asp (c.167T>A) in the general population?

DPH7 p.Val56Asp (c.167T>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about DPH7 p.Val56Asp (c.167T>A)?

AlphaMissense predicts likely benign (score 0.0843) — an in-silico prediction, not a clinical call.

DPH7 p.Val56Asp

c.167T>A · rs1410192531 · VCV2209686

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0843 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0843	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -5.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.1	GERP -2.5
Regional constraint	o/e 1.09	unconstrained · MANE · 24 kb · p 0.032 · regional, not allelic
Overall
CADD	2.402	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 0.01% Admixed American · 6/59,990 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000434% 7/1,613,706 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,998
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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: DPH7
Protein: p.Val56Asp
Coding: c.167T>A
MANE Select: NM_138778
dbSNP: rs1410192531
Type: single nucleotide variant
Location: chr9:137577590 (GRCh38)
Gene constraint: LOEUF 1.37 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.62

Full DPH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPH7 p.Ala105Thr Uncertain significance ★ ⚠ same type
DPH7 p.Ala16Thr Uncertain significance ★ ⚠ same type
DPH7 p.Ala193Val Uncertain significance ★ ⚠ same type
DPH7 p.Ala198Pro Uncertain significance ★ ⚠ same type
DPH7 p.Ala198Thr Uncertain significance ★ ⚠ same type
DPH7 p.Ala198Val Uncertain significance ★ ⚠ same type
DPH7 p.Ala427Thr Uncertain significance ★ ⚠ same type
DPH7 p.Arg237Ser Uncertain significance ★ ⚠ 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/dph7-p-val56asp (accessed [today's date]).

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