Is CIDEC p.Ile156Thr (c.467T>C) pathogenic?

CIDEC p.Ile156Thr (c.467T>C) is classified Uncertain significance in CIDEC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-08). AlphaMissense: likely benign (0.1253); Ultra-rare (popmax 0.04%, afr).

How common is CIDEC p.Ile156Thr (c.467T>C) in the general population?

CIDEC p.Ile156Thr (c.467T>C) is ultra-rare (popmax 0.04%, afr) (gnomAD).

What do computational predictors say about CIDEC p.Ile156Thr (c.467T>C)?

AlphaMissense predicts likely benign (score 0.1253) — an in-silico prediction, not a clinical call.

CIDEC p.Ile156Thr

c.467T>C · rs201709635 · VCV434768

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1253 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1253	likely benign
REVEL	0.756	pathogenic-leaning
SaProt	LLR -9.33	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 8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.98 · regional, not allelic
Overall
CADD	25.7	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 0.04% African / African-American · 30/75,060 alleles

Filtering AF 0.0288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00508% 82/1,614,216 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.04%	2,502
Remaining individualsnot grpmax-eligible	0.0352%	2,841
East Asian	0.0111%	8,977
Admixed American	0.00833%	12,003
South Asian	0.00439%	22,771
European (non-Finnish)	0.00136%	73,752

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.Ile156Thr
Coding: c.467T>C
MANE Select: NM_001321142
dbSNP: rs201709635
Type: single nucleotide variant
Location: chr3:9869969 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.19

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.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
CIDEC c.*162G>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-ile156thr (accessed [today's date]).

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