Is HYDIN p.Thr751= (c.2253C>T) pathogenic?

HYDIN p.Thr751= (c.2253C>T) is classified Likely benign in HYDIN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-07). Ultra-rare (popmax 0.0175%, afr); Associated with Inborn genetic diseases.

What condition is associated with HYDIN p.Thr751= (c.2253C>T)?

HYDIN p.Thr751= (c.2253C>T) is associated with Inborn genetic diseases (ClinVar).

How common is HYDIN p.Thr751= (c.2253C>T) in the general population?

HYDIN p.Thr751= (c.2253C>T) is ultra-rare (popmax 0.0175%, afr) (gnomAD).

HYDIN p.Thr751=

c.2253C>T · VCV3285127

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.56	GERP -1.5
Overall
CADD	0.737	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0175% African / African-American · 13/74,080 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00821%

Overall 0.00101% 16/1,577,858 alleles · ultra-rare exomes 11/1,425,760 · genomes 5/152,098 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0175%	5,698
Remaining individualsnot grpmax-eligible	0.00327%	30,537
Admixed American	0.00181%	55,230

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.Thr751=
Coding: c.2253C>T
MANE Select: NM_001270974
Type: single nucleotide variant
Location: chr16:71062292 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI <0.01 (gnomAD)
Residue 751: the 'interaction with kif9' region; 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.Thr751Ser Likely benign ★ same residue
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

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-thr751 (accessed [today's date]).

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