Is CALU p.Lys284= (c.852G>A) pathogenic?

CALU p.Lys284= (c.852G>A) is classified Likely benign in CALU (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). Very rare (popmax 0.00503%, amr).

How common is CALU p.Lys284= (c.852G>A) in the general population?

CALU p.Lys284= (c.852G>A) is very rare (popmax 0.00503%, amr) (gnomAD).

CALU p.Lys284=

c.852G>A · VCV4647854

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00503%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.035	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	phastCons 1
Overall
CADD	6.123	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00503% Admixed American · 3/59,678 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00067%

Overall 0.000374% 6/1,604,502 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00503%	19,893
African / African-American	0.00268%	37,342
Remaining individualsnot grpmax-eligible	0.00161%	62,134

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: CALU
Protein: p.Lys284=
Coding: c.852G>A
MANE Select: NM_001219
Type: single nucleotide variant
Location: chr7:128769071 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 79.82
Residue 284: a binding site; the ef-hand 6 domain

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

Similar variants

OPN1SW p.Ala309Pro Uncertain significance ★★ ⚠ same type
OPN1SW p.Ser335Phe Uncertain significance ★★ ⚠ same type
OPN1SW p.Ser324= Likely benign ★★ same type
OPN1SW p.Ser338= Benign/Likely benign ★★ same type
CALU p.Arg234Ter Likely pathogenic ★ same type
CALU c.-11-208C>G Uncertain significance ★ same type
CALU c.-3A>G Uncertain significance ★ same type
CALU c.*3456C>A 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/calu-p-lys284 (accessed [today's date]).

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