Is CALD1 p.Ala562Val (c.1685C>T) pathogenic?

CALD1 p.Ala562Val (c.1685C>T) is classified Likely benign in CALD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). AlphaMissense: ambiguous (0.4827); Rare (popmax 0.103%, nfe).

How common is CALD1 p.Ala562Val (c.1685C>T) in the general population?

CALD1 p.Ala562Val (c.1685C>T) is rare (popmax 0.103%, nfe) (gnomAD).

What do computational predictors say about CALD1 p.Ala562Val (c.1685C>T)?

AlphaMissense predicts ambiguous (score 0.4827) — an in-silico prediction, not a clinical call.

CALD1 p.Ala562Val

c.1685C>T · rs141179317 · VCV737584

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4827 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4827	ambiguous
REVEL	0.28	benign-leaning
SaProt	LLR -8.14	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 14 kb · p 0.061 · regional, not allelic
Overall
CADD	25.4	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 0.103% European (non-Finnish) · 1,205/1,166,772 alleles

Filtering AF 0.0984% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0964%

Overall 0.0819% 1,301/1,588,748 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.103%	968
Remaining individualsnot grpmax-eligible	0.073%	1,369
Admixed American	0.0431%	2,322
Middle Eastern	0.0166%	6,018
African / African-American	0.0148%	6,752
Finnishnot grpmax-eligible	0.0128%	7,815
South Asian	0.00794%	12,592

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.Ala562Val
Coding: c.1685C>T
MANE Select: NM_033138
dbSNP: rs141179317
Type: single nucleotide variant
Location: chr7:134947660 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 65.68
Residue 562: 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-ala562val (accessed [today's date]).

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