Is CALD1 p.Arg117Trp (c.349C>T) pathogenic?

CALD1 p.Arg117Trp (c.349C>T) is classified Uncertain significance in CALD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely pathogenic (0.5841); Very rare (popmax 0.00834%, amr).

How common is CALD1 p.Arg117Trp (c.349C>T) in the general population?

CALD1 p.Arg117Trp (c.349C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about CALD1 p.Arg117Trp (c.349C>T)?

AlphaMissense predicts likely pathogenic (score 0.5841) — an in-silico prediction, not a clinical call.

CALD1 p.Arg117Trp

c.349C>T · VCV4218286

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5841 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5841	likely pathogenic
REVEL	0.456	indeterminate
SaProt	LLR -13.28	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 1.4	GERP -3.9, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 65 kb · p 0.00033 · regional, not allelic
Overall
CADD	25.6	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

Grpmax group 0.00834% Admixed American · 5/59,950 alleles

Filtering AF 0.00358% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.00378% 61/1,613,548 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,990
European (non-Finnish)	0.00458%	21,851
Remaining individualsnot grpmax-eligible	0.0032%	31,238

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.Arg117Trp
Coding: c.349C>T
MANE Select: NM_033138
Type: single nucleotide variant
Location: chr7:134933118 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 65.68
Residue 117: the 'myosin and calmodulin-binding' region; the 'disordered' region

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-arg117trp (accessed [today's date]).

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