Is DHH p.Pro303Ser (c.907C>T) pathogenic?

DHH p.Pro303Ser (c.907C>T) is classified Uncertain significance in DHH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.1125); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DHH p.Pro303Ser (c.907C>T)?

DHH p.Pro303Ser (c.907C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DHH p.Pro303Ser (c.907C>T) in the general population?

DHH p.Pro303Ser (c.907C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DHH p.Pro303Ser (c.907C>T)?

AlphaMissense predicts likely benign (score 0.1125) — an in-silico prediction, not a clinical call.

DHH p.Pro303Ser

c.907C>T · VCV4240002

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1125 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1125	likely benign
REVEL	0.39	indeterminate
SaProt	LLR -8.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 4,650 bp · p 8.5e-08 · regional, not allelic
Overall
CADD	20.9	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

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: DHH
Protein: p.Pro303Ser
Coding: c.907C>T
MANE Select: NM_021044
Type: single nucleotide variant
Location: chr12:49090143 (GRCh38)
Gene constraint: LOEUF 0.999 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 5 PDB
Residue 303: a UniProt-annotated variant site (in gdmn; uncertain significance); a UniProt-annotated variant site (in gdmn)

Full DHH 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

DHH p.Pro303= Likely benign ★ same residue
DHH p.Arg102His Uncertain significance ★★ ⚠ same condition
DHH p.Ala193Val Uncertain significance ★ ⚠ same condition
DHH p.Ala291Thr Uncertain significance ★ ⚠ same condition
DHH p.Ala36Ser Uncertain significance ★ ⚠ same condition
DHH p.Arg102Cys Uncertain significance ★ ⚠ same condition
DHH p.Arg106Gln Uncertain significance ★ ⚠ same condition
DHH p.Arg156Pro 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/dhh-p-pro303ser (accessed [today's date]).

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