Is CDYL p.Val341Ile (c.1021G>A) pathogenic?

CDYL p.Val341Ile (c.1021G>A) is classified Uncertain significance in CDYL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely benign (0.2245); Ultra-rare (popmax 0.061%, nfe).

How common is CDYL p.Val341Ile (c.1021G>A) in the general population?

CDYL p.Val341Ile (c.1021G>A) is ultra-rare (popmax 0.061%, nfe) (gnomAD).

What do computational predictors say about CDYL p.Val341Ile (c.1021G>A)?

AlphaMissense predicts likely benign (score 0.2245) — an in-silico prediction, not a clinical call.

CDYL p.Val341Ile

c.1021G>A · rs145710209 · VCV2348889

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2245 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.061%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2245	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -8.27	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 9.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 17 kb · p 1.3e-25 · regional, not allelic
Overall
CADD	21.9	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 V395I vs ClinVar V341I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.061% European (non-Finnish) · 720/1,179,820 alleles

Filtering AF 0.0573% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0559%

Overall 0.0493% 795/1,613,660 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.061%	1,639
Remaining individualsnot grpmax-eligible	0.0448%	2,231
Ashkenazi Jewishnot grpmax-eligible	0.0237%	4,226
Finnishnot grpmax-eligible	0.0172%	5,822
Middle Eastern	0.0164%	6,082
East Asian	0.0134%	7,477
African / African-American	0.0107%	9,363
South Asian	0.00989%	10,116
Admixed American	0.00834%	11,989

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: CDYL
Protein: p.Val341Ile
Coding: c.1021G>A
MANE Select: NM_004824
dbSNP: rs145710209
Type: single nucleotide variant
Location: chr6:4937637 (GRCh38)
Gene constraint: LOEUF 0.293 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.33 · 3 PDB

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

Similar variants

CDYL p.Ala136Val Uncertain significance ★ ⚠ same type
CDYL p.Ala154Thr Uncertain significance ★ ⚠ same type
CDYL p.Ala182Ser Uncertain significance ★ ⚠ same type
CDYL p.Ala183Val Uncertain significance ★ ⚠ same type
CDYL p.Ala195Thr Uncertain significance ★ ⚠ same type
CDYL p.Ala329Thr Uncertain significance ★ ⚠ same type
CDYL p.Ala527Ser Uncertain significance ★ ⚠ same type
CDYL p.Arg11Lys 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/cdyl-p-val341ile (accessed [today's date]).

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