Is CYTH2 p.Ala385Val (c.1154C>T) pathogenic?

CYTH2 p.Ala385Val (c.1154C>T) is classified Uncertain significance in CYTH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-21). AlphaMissense: likely benign (0.1917); Very rare (popmax 0.00864%, nfe).

How common is CYTH2 p.Ala385Val (c.1154C>T) in the general population?

CYTH2 p.Ala385Val (c.1154C>T) is very rare (popmax 0.00864%, nfe) (gnomAD).

What do computational predictors say about CYTH2 p.Ala385Val (c.1154C>T)?

AlphaMissense predicts likely benign (score 0.1917) — an in-silico prediction, not a clinical call.

CYTH2 p.Ala385Val

c.1154C>T · rs759539903 · VCV2341084

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1917 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00864%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1917	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -11.20	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 9,699 bp · p 1.7e-11 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A386V vs ClinVar A385V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00864% European (non-Finnish) · 102/1,179,972 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00676%

Overall 0.00651% 105/1,613,922 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00864%	11,568
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00134%	74,888
South Asian	0.0011%	91,092

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.Ala385Val
Coding: c.1154C>T
MANE Select: NM_004228
dbSNP: rs759539903
Type: single nucleotide variant
Location: chr19:48479164 (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.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
CYTH2 p.Arg98His 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-ala385val (accessed [today's date]).

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