Is CIDEA p.Leu93Val (c.277T>G) pathogenic?

CIDEA p.Leu93Val (c.277T>G) is classified Benign in CIDEA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-06). AlphaMissense: likely benign (0.1856); Low-frequency (popmax 1.9%, afr).

How common is CIDEA p.Leu93Val (c.277T>G) in the general population?

CIDEA p.Leu93Val (c.277T>G) is low-frequency (popmax 1.9%, afr) (gnomAD).

What do computational predictors say about CIDEA p.Leu93Val (c.277T>G)?

AlphaMissense predicts likely benign (score 0.1856) — an in-silico prediction, not a clinical call.

CIDEA p.Leu93Val

c.277T>G · rs116777437 · VCV731469

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1856 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.9%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1856	likely benign
REVEL	0.436	indeterminate
SaProt	LLR -11.04	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 -0.5	GERP -3.7, phastCons 0.022
Regional constraint	o/e 1.05	unconstrained · MANE · 23 kb · p 0.35 · regional, not allelic
Overall
CADD	17.52	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 1.9% African / African-American · 1,425/75,028 alleles

Filtering AF 1.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.78%

Overall 0.0964% 1,556/1,614,052 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.9%	53
Remaining individualsnot grpmax-eligible	0.109%	919
Admixed American	0.0733%	1,364
Middle Eastern	0.0495%	2,020
South Asian	0.00769%	13,009
European (non-Finnish)	0.000763%	131,106

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: CIDEA
Protein: p.Leu93Val
Coding: c.277T>G
MANE Select: NM_001279
dbSNP: rs116777437
Type: single nucleotide variant
Location: chr18:12264400 (GRCh38)
Gene constraint: LOEUF 1.027 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.69 · 1 PDB
Residue 93: the cide-n domain

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

Similar variants

CIDEA p.Ala127Gly Uncertain significance ★ ⚠ same type
CIDEA p.Ala181Asp Uncertain significance ★ ⚠ same type
CIDEA p.Ala181Val Uncertain significance ★ ⚠ same type
CIDEA p.Arg128Thr Uncertain significance ★ ⚠ same type
CIDEA p.Arg162Trp Uncertain significance ★ ⚠ same type
CIDEA p.Arg175Gln Uncertain significance ★ ⚠ same type
CIDEA p.Arg175Trp Uncertain significance ★ ⚠ same type
CIDEA p.Arg197Gln Uncertain significance ★ ⚠ 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/cidea-p-leu93val (accessed [today's date]).

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