Is CIDEC p.Arg52Gln (c.155G>A) pathogenic?

CIDEC p.Arg52Gln (c.155G>A) is classified Uncertain significance in CIDEC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-24). AlphaMissense: likely benign (0.2355); Ultra-rare (popmax 0.0431%, amr).

How common is CIDEC p.Arg52Gln (c.155G>A) in the general population?

CIDEC p.Arg52Gln (c.155G>A) is ultra-rare (popmax 0.0431%, amr) (gnomAD).

What do computational predictors say about CIDEC p.Arg52Gln (c.155G>A)?

AlphaMissense predicts likely benign (score 0.2355) — an in-silico prediction, not a clinical call.

CIDEC p.Arg52Gln

c.155G>A · rs754291958 · VCV2208593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2355 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0431%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2355	likely benign
REVEL	0.391	indeterminate
SaProt	LLR -12.87	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.98 · regional, not allelic
Overall
CADD	25.1	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 0.0431% Admixed American · 22/51,080 alleles

Filtering AF 0.0291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0245%

Overall 0.00277% 43/1,553,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0431%	2,322
African / African-American	0.00682%	14,661
Remaining individualsnot grpmax-eligible	0.00665%	15,047
European (non-Finnish)	0.00105%	95,643

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.Arg52Gln
Coding: c.155G>A
MANE Select: NM_001321142
dbSNP: rs754291958
Type: single nucleotide variant
Location: chr3:9877118 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.19
Residue 52: 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-arg52gln (accessed [today's date]).

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