Is HYDIN p.Ser511Arg (c.1533T>A) pathogenic?

HYDIN p.Ser511Arg (c.1533T>A) is classified Uncertain significance in HYDIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: ambiguous (0.3487); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with HYDIN p.Ser511Arg (c.1533T>A)?

HYDIN p.Ser511Arg (c.1533T>A) is associated with Inborn genetic diseases (ClinVar).

How common is HYDIN p.Ser511Arg (c.1533T>A) in the general population?

HYDIN p.Ser511Arg (c.1533T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HYDIN p.Ser511Arg (c.1533T>A)?

AlphaMissense predicts ambiguous (score 0.3487) — an in-silico prediction, not a clinical call.

HYDIN p.Ser511Arg

c.1533T>A · VCV4036953

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3487 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3487	ambiguous
REVEL	0.169	moderately benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.37	acceptor gain · deltas
Pangolin	Δ0.23	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.043	GERP -1.8
Regional constraint	o/e 0.60	unconstrained · MANE · 73 kb · p 7.8e-09 · regional, not allelic
Overall
CADD	14.21	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.Ser511Arg
Coding: c.1533T>A
MANE Select: NM_001270974
Type: single nucleotide variant
Location: chr16:71088438 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI <0.01 (gnomAD)
Residue 511: the 'interaction with kif9' region; a β-strand; 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-ser511arg (accessed [today's date]).

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