Is CIDEC p.Met59Val (c.175A>G) pathogenic?

CIDEC p.Met59Val (c.175A>G) is classified Benign/Likely benign in CIDEC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-12). AlphaMissense: likely benign (0.0795); Low-frequency (popmax 1.01%, eas).

How common is CIDEC p.Met59Val (c.175A>G) in the general population?

CIDEC p.Met59Val (c.175A>G) is low-frequency (popmax 1.01%, eas) (gnomAD).

What do computational predictors say about CIDEC p.Met59Val (c.175A>G)?

AlphaMissense predicts likely benign (score 0.0795) — an in-silico prediction, not a clinical call.

CIDEC p.Met59Val

c.175A>G · rs200343387 · VCV713900

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0795 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.01%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0795	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.46	GERP -0.81, phastCons 0.2
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.98 · regional, not allelic
Overall
CADD	3.075	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 1.01% East Asian · 416/41,298 alleles

Filtering AF 0.927% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.896%

Overall 0.0315% 490/1,553,616 alleles · low-frequency exomes 414/1,401,274 · genomes 76/152,342 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.01%	99
Remaining individualsnot grpmax-eligible	0.0731%	1,368
South Asian	0.0321%	3,117
European (non-Finnish)	0.000261%	382,643

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.Met59Val
Coding: c.175A>G
MANE Select: NM_001321142
dbSNP: rs200343387
Type: single nucleotide variant
Location: chr3:9877098 (GRCh38)
Gene constraint: LOEUF 0.927 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 74.19
Residue 59: 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-met59val (accessed [today's date]).

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