Is CALD1 p.Lys360= (c.1080A>G) pathogenic?

CALD1 p.Lys360= (c.1080A>G) is classified Likely benign in CALD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Very rare (popmax 0.00819%, afr).

How common is CALD1 p.Lys360= (c.1080A>G) in the general population?

CALD1 p.Lys360= (c.1080A>G) is very rare (popmax 0.00819%, afr) (gnomAD).

CALD1 p.Lys360=

c.1080A>G · rs529198474 · VCV759456

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00819%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.038	GERP -2, phastCons 0.19
Overall
CADD	0.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00819% African / African-American · 6/73,242 alleles

Filtering AF 0.00354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.00399% 64/1,602,510 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0204%	4,897
Remaining individualsnot grpmax-eligible	0.0113%	8,875
African / African-Americangrpmax	0.00819%	12,207
Admixed American	0.00686%	14,579
East Asian	0.0045%	22,204
European (non-Finnish)	0.00315%	31,749
Finnishnot grpmax-eligible	0.00158%	63,448
South Asian	0.00111%	90,040

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CALD1
Protein: p.Lys360=
Coding: c.1080A>G
MANE Select: NM_033138
dbSNP: rs529198474
Type: single nucleotide variant
Location: chr7:134933849 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 65.68
Residue 360: the 'disordered' region; the '3 x 14 aa tandem repeats of e-e-e-k-r-a-a-e-e-r-q-r-i-k' region

Full CALD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CALD1 p.Lys360Ile Uncertain significance ★ ⚠ same residue
CALD1 p.Ala324Glu Benign ★★ ⚠ same type
CALD1 p.Asp122Asn Likely benign ★★ ⚠ same type
CALD1 p.Glu77Lys Benign ★★ ⚠ same type
CALD1 p.Ile671Val Benign ★★ same type
CALD1 p.Met257Ile Likely benign ★★ same type
CALD1 p.Ser171Phe Benign ★★ ⚠ same type
CALD1 p.Ala265Thr 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/cald1-p-lys360 (accessed [today's date]).

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