Is CCNYL1 p.Ala338Thr (c.1012G>A) pathogenic?

CCNYL1 p.Ala338Thr (c.1012G>A) is classified Uncertain significance in CCNYL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely benign (0.0945); Ultra-rare (popmax 0.0363%, sas).

How common is CCNYL1 p.Ala338Thr (c.1012G>A) in the general population?

CCNYL1 p.Ala338Thr (c.1012G>A) is ultra-rare (popmax 0.0363%, sas) (gnomAD).

What do computational predictors say about CCNYL1 p.Ala338Thr (c.1012G>A)?

AlphaMissense predicts likely benign (score 0.0945) — an in-silico prediction, not a clinical call.

CCNYL1 p.Ala338Thr

c.1012G>A · VCV4650156

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0945 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0363%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0945	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -5.87	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 8.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 2,725 bp · p 0.41 · regional, not allelic
Overall
CADD	22.1	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0363% South Asian · 33/90,954 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0232%

Overall 0.00564% 91/1,612,760 alleles · ultra-rare exomes 86/1,461,024 · genomes 5/151,736 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0363%	2,756
East Asian	0.0223%	4,482
European (non-Finnish)	0.00382%	26,206
Remaining individualsnot grpmax-eligible	0.0032%	31,222
Admixed American	0.00167%	59,942

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: CCNYL1
Protein: p.Ala338Thr
Coding: c.1012G>A
MANE Select: NM_001330218
Type: single nucleotide variant
Location: chr2:207753630 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 75.10

Full CCNYL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCNYL1 p.Ala24Val Uncertain significance ★ ⚠ same type
CCNYL1 p.Ala345Val Uncertain significance ★ ⚠ same type
CCNYL1 p.Ala44Thr Uncertain significance ★ ⚠ same type
CCNYL1 p.Arg20Cys Uncertain significance ★ ⚠ same type
CCNYL1 p.Arg299Cys Uncertain significance ★ ⚠ same type
CCNYL1 p.Arg340Gly Uncertain significance ★ ⚠ same type
CCNYL1 p.Arg353His Uncertain significance ★ ⚠ same type
CCNYL1 p.Asp54Tyr 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/ccnyl1-p-ala338thr (accessed [today's date]).

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