Is HYDIN p.Arg3306Gln (c.9917G>A) pathogenic?

HYDIN p.Arg3306Gln (c.9917G>A) is classified Uncertain significance in HYDIN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-22). AlphaMissense: likely benign (0.2782); Very rare (popmax 0.00769%, sas).

How common is HYDIN p.Arg3306Gln (c.9917G>A) in the general population?

HYDIN p.Arg3306Gln (c.9917G>A) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about HYDIN p.Arg3306Gln (c.9917G>A)?

AlphaMissense predicts likely benign (score 0.2782) — an in-silico prediction, not a clinical call.

HYDIN p.Arg3306Gln

c.9917G>A · VCV4930842

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2782 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.2782	likely benign
REVEL	0.191	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 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 11 kb · p 0.0003 · regional, not allelic
Overall
CADD	23.4	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 0.00769% South Asian · 7/91,086 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00285% 46/1,614,126 alleles · very rare exomes 38/1,461,886 · genomes 8/152,240 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
Remaining individualsnot grpmax-eligible	0.0064%	15,627
African / African-American	0.00534%	18,740
European (non-Finnish)	0.00263%	38,066

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.Arg3306Gln
Coding: c.9917G>A
MANE Select: NM_001270974
Type: single nucleotide variant
Location: chr16:70883982 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI <0.01 (gnomAD)
Residue 3306: a UniProt-annotated variant site (in cild5; uncertain significance); a UniProt-annotated variant site (in cild5; likely pathogenic; absence of spef2 in ciliary axonemes of respiratory cells)

Full HYDIN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HYDIN c.12444-1G>A Likely pathogenic ★★ same type
HYDIN c.12444-3C>G Likely pathogenic ★★ same type
HYDIN c.6669+1G>A Likely pathogenic ★★ same type
HYDIN p.Arg2120Ter Likely pathogenic ★★ same type
HYDIN p.Arg444Ter Pathogenic/Likely pathogenic ★★ same type
HYDIN p.Glu683Ter Pathogenic/Likely pathogenic ★★ same type
HYDIN p.Tyr599Ter Pathogenic/Likely pathogenic ★★ same type
HYDIN p.Arg163Gln Uncertain significance ★★ ⚠ same type

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-arg3306gln (accessed [today's date]).

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