Is HYDIN p.Pro2011Ser (c.6031C>T) pathogenic?

HYDIN p.Pro2011Ser (c.6031C>T) is classified Uncertain significance in HYDIN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-23). AlphaMissense: likely pathogenic (0.8141); Very rare (popmax 0.000149%, nfe); Associated with Inborn genetic diseases.

What condition is associated with HYDIN p.Pro2011Ser (c.6031C>T)?

HYDIN p.Pro2011Ser (c.6031C>T) is associated with Inborn genetic diseases (ClinVar).

How common is HYDIN p.Pro2011Ser (c.6031C>T) in the general population?

HYDIN p.Pro2011Ser (c.6031C>T) is very rare (popmax 0.000149%, nfe) (gnomAD).

What do computational predictors say about HYDIN p.Pro2011Ser (c.6031C>T)?

AlphaMissense predicts likely pathogenic (score 0.8141) — an in-silico prediction, not a clinical call.

HYDIN p.Pro2011Ser

c.6031C>T · rs2078352358 · VCV2246806

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8141 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000149%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8141	likely pathogenic
REVEL	0.384	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.26	constrained · MANE · 5,214 bp · p 2.9e-22 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000149% European (non-Finnish) · 1/670,330 alleles

Overall 0.000103% 1/974,120 alleles · very rare exomes 0/839,874 · genomes 1/134,246 · joint denominator

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: HYDIN
Protein: p.Pro2011Ser
Coding: c.6031C>T
MANE Select: NM_001270974
dbSNP: rs2078352358
Type: single nucleotide variant
Location: chr16:70959758 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI <0.01 (gnomAD)
Residue 2011: a UniProt-annotated variant site (in cild5; uncertain significance)

Full HYDIN 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

HYDIN p.Arg5Ile Uncertain significance ★★ ⚠ same condition
HYDIN p.Arg777Gly Uncertain significance ★★ ⚠ same condition
HYDIN p.Asn125Tyr Uncertain significance ★★ ⚠ same condition
HYDIN p.Asn2915Ser Uncertain significance ★★ ⚠ same condition
HYDIN p.Asn387His Uncertain significance ★★ ⚠ same condition
HYDIN p.Glu410Ala Uncertain significance ★★ ⚠ same condition
HYDIN p.Gly681Arg Uncertain significance ★★ same condition
HYDIN p.Pro2991Thr 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/hydin-p-pro2011ser (accessed [today's date]).

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