Is CYTH2 p.Gln360Arg (c.1079A>G) pathogenic?

CYTH2 p.Gln360Arg (c.1079A>G) is classified Uncertain significance in CYTH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-23). AlphaMissense: likely benign (0.0816); Ultra-rare (popmax 0.032%, afr).

How common is CYTH2 p.Gln360Arg (c.1079A>G) in the general population?

CYTH2 p.Gln360Arg (c.1079A>G) is ultra-rare (popmax 0.032%, afr) (gnomAD).

What do computational predictors say about CYTH2 p.Gln360Arg (c.1079A>G)?

AlphaMissense predicts likely benign (score 0.0816) — an in-silico prediction, not a clinical call.

CYTH2 p.Gln360Arg

c.1079A>G · VCV4009107

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0816 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0816	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -3.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -3.6, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 9,699 bp · p 1.7e-11 · regional, not allelic
Overall
CADD	23.1	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 and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q361R vs ClinVar Q360R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.032% African / African-American · 24/74,900 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.00161% 26/1,613,442 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.032%	3,121
Admixed American	0.00167%	59,952
European (non-Finnish)	8.48e-05%	1,179,770

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: CYTH2
Protein: p.Gln360Arg
Coding: c.1079A>G
MANE Select: NM_004228
Type: single nucleotide variant
Location: chr19:48478559 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 85.02 · 11 PDB
Residue 360: the ph domain

Full CYTH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYTH2 p.Ala168Thr Uncertain significance ★ ⚠ same type
CYTH2 p.Ala385Val Uncertain significance ★ ⚠ same type
CYTH2 p.Arg212His Uncertain significance ★ ⚠ same type
CYTH2 p.Arg232Thr Uncertain significance ★ ⚠ same type
CYTH2 p.Arg262Gln Uncertain significance ★ ⚠ same type
CYTH2 p.Arg344Gln Uncertain significance ★ ⚠ same type
CYTH2 p.Arg35Cys Uncertain significance ★ ⚠ same type
CYTH2 p.Arg61Gln 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/cyth2-p-gln360arg (accessed [today's date]).

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