Is CIDEC p.Arg43Trp (c.127C>T) pathogenic?

CIDEC p.Arg43Trp (c.127C>T) is classified Uncertain significance in CIDEC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-27). AlphaMissense: likely benign (0.1214); Very rare (popmax 0.00821%, afr).

How common is CIDEC p.Arg43Trp (c.127C>T) in the general population?

CIDEC p.Arg43Trp (c.127C>T) is very rare (popmax 0.00821%, afr) (gnomAD).

What do computational predictors say about CIDEC p.Arg43Trp (c.127C>T)?

AlphaMissense predicts likely benign (score 0.1214) — an in-silico prediction, not a clinical call.

CIDEC p.Arg43Trp

c.127C>T · rs988262334 · VCV2393147

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1214 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00821%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1214	likely benign
REVEL	0.525	indeterminate
SaProt	LLR -10.40	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 8	GERP 0.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.98 · regional, not allelic
Overall
CADD	26.6	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 0.00821% African / African-American · 6/73,102 alleles

Filtering AF 0.00613% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00565%

Overall 0.00612% 95/1,551,526 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00821%	12,184
European (non-Finnish)	0.00741%	13,495
Remaining individualsnot grpmax-eligible	0.00333%	30,040
Finnishnot grpmax-eligible	0.00167%	59,932
South Asian	0.00119%	84,072

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.Arg43Trp
Coding: c.127C>T
MANE Select: NM_001321142
dbSNP: rs988262334
Type: single nucleotide variant
Location: chr3:9877146 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.19
Residue 43: the cide-n domain

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

Similar variants

CIDEC p.Arg43Gln Uncertain significance ★ ⚠ same residue
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

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-arg43trp (accessed [today's date]).

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