Is DPH3 p.Asp12Ala (c.35A>C) pathogenic?

DPH3 p.Asp12Ala (c.35A>C) is classified Uncertain significance in DPH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely pathogenic (0.9906); Ultra-rare (popmax 0.0516%, amr).

How common is DPH3 p.Asp12Ala (c.35A>C) in the general population?

DPH3 p.Asp12Ala (c.35A>C) is ultra-rare (popmax 0.0516%, amr) (gnomAD).

What do computational predictors say about DPH3 p.Asp12Ala (c.35A>C)?

AlphaMissense predicts likely pathogenic (score 0.9906) — an in-silico prediction, not a clinical call.

DPH3 p.Asp12Ala

c.35A>C · VCV4014565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9906 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0516%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9906	likely pathogenic
REVEL	0.547	indeterminate
SaProt	LLR -14.17	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 4,109 bp · p 0.77 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0516% Admixed American · 31/60,034 alleles

Filtering AF 0.0374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0325%

Overall 0.00192% 31/1,614,214 alleles · ultra-rare

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: DPH3
Protein: p.Asp12Ala
Coding: c.35A>C
MANE Select: NM_206831
Type: single nucleotide variant
Location: chr3:16264842 (GRCh38)
Gene constraint: LOEUF 1.439 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.51 · 1 PDB
Residue 12: the dph-type mb domain; a turn

Full DPH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPH3 p.Asp18Gly Uncertain significance ★ ⚠ same type
DPH3 p.Asp62Asn Uncertain significance ★ ⚠ same type
DPH3 p.Cys28Arg Uncertain significance ★ ⚠ same type
DPH3 p.Cys51Ser Uncertain significance ★ ⚠ same type
DPH3 p.Lys36Arg Uncertain significance ★ ⚠ same type
DPH3 p.Pro25Leu Uncertain significance ★ ⚠ same type
DPH3 p.Thr21Ser Uncertain significance ★ ⚠ same type
DPH3 p.Thr47Lys 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/dph3-p-asp12ala (accessed [today's date]).

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