Is CIDEC p.Val22Leu (c.64G>T) pathogenic?

CIDEC p.Val22Leu (c.64G>T) is classified Uncertain significance in CIDEC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.1436); Very rare (popmax 0.00685%, afr).

How common is CIDEC p.Val22Leu (c.64G>T) in the general population?

CIDEC p.Val22Leu (c.64G>T) is very rare (popmax 0.00685%, afr) (gnomAD).

What do computational predictors say about CIDEC p.Val22Leu (c.64G>T)?

AlphaMissense predicts likely benign (score 0.1436) — an in-silico prediction, not a clinical call.

CIDEC p.Val22Leu

c.64G>T · VCV4002988

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1436 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00685%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1436	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -5.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.32	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.1	GERP 1.4, phastCons 0.92
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.98 · regional, not allelic
Overall
CADD	16.97	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 0.00685% African / African-American · 5/73,012 alleles

Filtering AF 0.0026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00165%

Overall 0.000323% 5/1,550,130 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: CIDEC
Protein: p.Val22Leu
Coding: c.64G>T
MANE Select: NM_001321142
Type: single nucleotide variant
Location: chr3:9877209 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.19
Residue 22: the 'required for liquid-liquid phase separation (llps)' region

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

Similar variants

CIDEC p.Arg182His Uncertain significance ★★ ⚠ same type
CIDEC p.Ile156Thr Uncertain significance ★★ ⚠ same type
CIDEC p.Met195Ile Uncertain significance ★★ ⚠ same type
CIDEC p.Val54Met Uncertain significance ★★ ⚠ same type
CIDEC c.207+180G>A Benign ★★ same type
CIDEC c.208-91C>T Benign ★★ same type
CIDEC c.53+77T>A Benign ★★ same type
CIDEC c.-25-52G>T Benign ★★ 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/cidec-p-val22leu (accessed [today's date]).

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