Is CALCOCO2 p.Glu318Lys (c.952G>A) pathogenic?

CALCOCO2 p.Glu318Lys (c.952G>A) is classified Likely benign in CALCOCO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely benign (0.0589); Very rare (popmax 0.00503%, nfe).

How common is CALCOCO2 p.Glu318Lys (c.952G>A) in the general population?

CALCOCO2 p.Glu318Lys (c.952G>A) is very rare (popmax 0.00503%, nfe) (gnomAD).

What do computational predictors say about CALCOCO2 p.Glu318Lys (c.952G>A)?

AlphaMissense predicts likely benign (score 0.0589) — an in-silico prediction, not a clinical call.

CALCOCO2 p.Glu318Lys

c.952G>A · rs781375670 · VCV2205689

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0589 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00503%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0589	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -6.22	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 3.3	GERP -2, phastCons 0.99
Regional constraint	o/e 0.82	unconstrained · MANE · 10 kb · p 0.0082 · regional, not allelic
Overall
CADD	12.64	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 0.00503% European (non-Finnish) · 59/1,172,616 alleles

Filtering AF 0.00396% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00363%

Overall 0.00387% 62/1,604,024 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00503%	19,875
East Asian	0.00223%	44,816
Remaining individualsnot grpmax-eligible	0.00161%	62,048
African / African-American	0.00134%	74,682

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: CALCOCO2
Protein: p.Glu318Lys
Coding: c.952G>A
MANE Select: NM_005831
dbSNP: rs781375670
Type: single nucleotide variant
Location: chr17:48856131 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.16 · 10 PDB

Full CALCOCO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CALCOCO2 p.His267Arg Uncertain significance ★★ ⚠ same type
CALCOCO2 p.Ala175Val Uncertain significance ★ ⚠ same type
CALCOCO2 p.Ala323Asp Uncertain significance ★ ⚠ same type
CALCOCO2 p.Ala375Thr Uncertain significance ★ ⚠ same type
CALCOCO2 p.Arg117Gln Uncertain significance ★ ⚠ same type
CALCOCO2 p.Arg117Trp Uncertain significance ★ ⚠ same type
CALCOCO2 p.Arg126Cys Uncertain significance ★ ⚠ same type
CALCOCO2 p.Arg51His 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/calcoco2-p-glu318lys (accessed [today's date]).

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