Is CYTH2 p.Asp3Glu (c.9C>A) pathogenic?

CYTH2 p.Asp3Glu (c.9C>A) is classified Uncertain significance in CYTH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). AlphaMissense: likely benign (0.0768); Very rare (popmax 0.00463%, afr).

How common is CYTH2 p.Asp3Glu (c.9C>A) in the general population?

CYTH2 p.Asp3Glu (c.9C>A) is very rare (popmax 0.00463%, afr) (gnomAD).

What do computational predictors say about CYTH2 p.Asp3Glu (c.9C>A)?

AlphaMissense predicts likely benign (score 0.0768) — an in-silico prediction, not a clinical call.

CYTH2 p.Asp3Glu

c.9C>A · VCV3270735

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0768 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00463%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0768	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -5.86	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 5.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 9,699 bp · p 1.7e-11 · regional, not allelic
Overall
CADD	23.8	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00463% African / African-American · 3/64,768 alleles

Filtering AF 0.00123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000641%

Overall 0.000226% 3/1,327,084 alleles · very rare

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.Asp3Glu
Coding: c.9C>A
MANE Select: NM_004228
Type: single nucleotide variant
Location: chr19:48469516 (GRCh38)
Gene constraint: LOEUF 0.597 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 85.02 · 11 PDB

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-asp3glu (accessed [today's date]).

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