Is CIDEC p.Leu85Val (c.253C>G) pathogenic?

CIDEC p.Leu85Val (c.253C>G) is classified Uncertain significance in CIDEC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely benign (0.26); Very rare (popmax 0.00186%, nfe).

How common is CIDEC p.Leu85Val (c.253C>G) in the general population?

CIDEC p.Leu85Val (c.253C>G) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about CIDEC p.Leu85Val (c.253C>G)?

AlphaMissense predicts likely benign (score 0.26) — an in-silico prediction, not a clinical call.

CIDEC p.Leu85Val

c.253C>G · VCV4653805

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.26 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.26	likely benign
REVEL	0.655	pathogenic-leaning
SaProt	LLR -8.96	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 0.81, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.98 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 22/1,180,048 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,614,032 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.Leu85Val
Coding: c.253C>G
MANE Select: NM_001321142
Type: single nucleotide variant
Location: chr3:9870277 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.19
Residue 85: the cide-n domain

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-leu85val (accessed [today's date]).

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