Is HYDIN p.Pro48Ser (c.142C>T) pathogenic?

HYDIN p.Pro48Ser (c.142C>T) is classified Uncertain significance in HYDIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely pathogenic (0.8539); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with HYDIN p.Pro48Ser (c.142C>T)?

HYDIN p.Pro48Ser (c.142C>T) is associated with Inborn genetic diseases (ClinVar).

How common is HYDIN p.Pro48Ser (c.142C>T) in the general population?

HYDIN p.Pro48Ser (c.142C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HYDIN p.Pro48Ser (c.142C>T)?

AlphaMissense predicts likely pathogenic (score 0.8539) — an in-silico prediction, not a clinical call.

HYDIN p.Pro48Ser

c.142C>T · VCV4621890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8539 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8539	likely pathogenic · top 10% in HYDIN
REVEL	0.333	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 11 kb · p 0.4 · regional, not allelic
Overall
CADD	23.3	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

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: HYDIN
Protein: p.Pro48Ser
Coding: c.142C>T
MANE Select: NM_001270974
Type: single nucleotide variant
Location: chr16:71184984 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI <0.01 (gnomAD)

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-pro48ser (accessed [today's date]).

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