Is DPH3 p.Cys51Ser (c.151T>A) pathogenic?

DPH3 p.Cys51Ser (c.151T>A) is classified Uncertain significance in DPH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely pathogenic (0.9989); Absent from gnomAD v4.1.

How common is DPH3 p.Cys51Ser (c.151T>A) in the general population?

DPH3 p.Cys51Ser (c.151T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPH3 p.Cys51Ser (c.151T>A)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

DPH3 p.Cys51Ser

c.151T>A · VCV4244422

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic · top 4% in DPH3
REVEL	0.925	moderately pathogenic-leaning
SaProt	LLR -12.17	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 4,109 bp · p 0.77 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPH3
Protein: p.Cys51Ser
Coding: c.151T>A
MANE Select: NM_206831
Type: single nucleotide variant
Location: chr3:16264187 (GRCh38)
Gene constraint: LOEUF 1.439 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.51 · 1 PDB
Residue 51: the dph-type mb domain; a turn; a binding site

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

Similar variants

DPH3 p.Asp12Ala Uncertain significance ★ ⚠ same type
DPH3 p.Asp18Gly Uncertain significance ★ ⚠ same type
DPH3 p.Asp62Asn Uncertain significance ★ ⚠ same type
DPH3 p.Cys28Arg 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-cys51ser (accessed [today's date]).

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