Is DOHH p.Pro20Ser (c.58C>T) pathogenic?

DOHH p.Pro20Ser (c.58C>T) is classified Uncertain significance in DOHH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-21). AlphaMissense: likely benign (0.116); Very rare (popmax 0.00153%, nfe).

How common is DOHH p.Pro20Ser (c.58C>T) in the general population?

DOHH p.Pro20Ser (c.58C>T) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about DOHH p.Pro20Ser (c.58C>T)?

AlphaMissense predicts likely benign (score 0.116) — an in-silico prediction, not a clinical call.

DOHH p.Pro20Ser

c.58C>T · rs767989996 · VCV2405316

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.116 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.116	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -7.88	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 5.1	GERP 1.2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 5,319 bp · p 0.98 · regional, not allelic
Overall
CADD	19.59	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 0.00153% European (non-Finnish) · 18/1,178,684 alleles

Filtering AF 0.000954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00112% 18/1,608,980 alleles · very 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: DOHH
Protein: p.Pro20Ser
Coding: c.58C>T
MANE Select: NM_001145165
dbSNP: rs767989996
Type: single nucleotide variant
Location: chr19:3496757 (GRCh38)
Gene constraint: LOEUF 1.688 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.13 · 2 PDB

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

Similar variants

DOHH p.Ala250Thr Uncertain significance ★★ same type
DOHH p.Arg160Cys Uncertain significance ★★ ⚠ same type
DOHH p.Gly159= Likely benign ★★ same type
DOHH p.Ala153Gly Uncertain significance ★ ⚠ same type
DOHH p.Ala153Thr Uncertain significance ★ ⚠ same type
DOHH p.Ala164Val Uncertain significance ★ ⚠ same type
DOHH p.Ala181Ser Uncertain significance ★ ⚠ same type
DOHH p.Ala191Val 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/dohh-p-pro20ser (accessed [today's date]).

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