Is HYDIN p.Val755Phe (c.2263G>T) pathogenic?

HYDIN p.Val755Phe (c.2263G>T) is classified Uncertain significance in HYDIN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.1098); Very rare (popmax 0.00554%, amr); Associated with Inborn genetic diseases.

What condition is associated with HYDIN p.Val755Phe (c.2263G>T)?

HYDIN p.Val755Phe (c.2263G>T) is associated with Inborn genetic diseases (ClinVar).

How common is HYDIN p.Val755Phe (c.2263G>T) in the general population?

HYDIN p.Val755Phe (c.2263G>T) is very rare (popmax 0.00554%, amr) (gnomAD).

What do computational predictors say about HYDIN p.Val755Phe (c.2263G>T)?

AlphaMissense predicts likely benign (score 0.1098) — an in-silico prediction, not a clinical call.

HYDIN p.Val755Phe

c.2263G>T · rs756524075 · VCV3107729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1098 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00554%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1098	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -5.1
Regional constraint	o/e 0.34	constrained · MANE · 37 kb · p 1e-26 · regional, not allelic
Overall
CADD	3.614	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00554% Admixed American · 3/54,160 alleles

Filtering AF 0.00147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000707%

Overall 0.000574% 9/1,568,428 alleles · very rare exomes 6/1,416,264 · genomes 3/152,164 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00554%	18,053
Remaining individualsnot grpmax-eligible	0.00164%	60,802
European (non-Finnish)	0.000433%	230,779

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.Val755Phe
Coding: c.2263G>T
MANE Select: NM_001270974
dbSNP: rs756524075
Type: single nucleotide variant
Location: chr16:71062282 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI <0.01 (gnomAD)
Residue 755: 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-val755phe (accessed [today's date]).

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