Is CALD1 p.Glu707Asp (c.2121A>C) pathogenic?

CALD1 p.Glu707Asp (c.2121A>C) is classified Uncertain significance in CALD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.1615); Ultra-rare (popmax 0.033%, mid).

How common is CALD1 p.Glu707Asp (c.2121A>C) in the general population?

CALD1 p.Glu707Asp (c.2121A>C) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CALD1 p.Glu707Asp (c.2121A>C)?

AlphaMissense predicts likely benign (score 0.1615) — an in-silico prediction, not a clinical call.

CALD1 p.Glu707Asp

c.2121A>C · VCV4647770

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1615 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1615	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -3.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 21 kb · p 0.00018 · regional, not allelic
Overall
CADD	12.48	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.0039% 63/1,614,174 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0192%	5,209
African / African-American	0.00533%	18,763
European (non-Finnish)	0.00373%	26,818
South Asian	0.0011%	91,080

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.Glu707Asp
Coding: c.2121A>C
MANE Select: NM_033138
Type: single nucleotide variant
Location: chr7:134960033 (GRCh38)
Gene constraint: LOEUF 0.498 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 65.68

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-glu707asp (accessed [today's date]).

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