Is CALD1 p.Arg12Ser (c.36G>T) pathogenic?

CALD1 p.Arg12Ser (c.36G>T) is classified Uncertain significance in CALD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-04). AlphaMissense: likely pathogenic (0.9983); Absent from gnomAD v4.1.

How common is CALD1 p.Arg12Ser (c.36G>T) in the general population?

CALD1 p.Arg12Ser (c.36G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CALD1 p.Arg12Ser (c.36G>T)?

AlphaMissense predicts likely pathogenic (score 0.9983) — an in-silico prediction, not a clinical call.

CALD1 p.Arg12Ser

c.36G>T · VCV3484375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9983 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9983	likely pathogenic · top 1% in CALD1
REVEL	0.305	indeterminate
SaProt	LLR -14.63	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -0.71, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 65 kb · p 0.00033 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CALD1
Protein: p.Arg12Ser
Coding: c.36G>T
MANE Select: NM_033138
Type: single nucleotide variant
Location: chr7:134867769 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 65.68
Residue 12: a modified residue (phosphoserine)

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

Similar variants

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
CALD1 p.Ala282Val 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-arg12ser (accessed [today's date]).

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