Is CALCR p.Ala429Ser (c.1285G>T) pathogenic?

CALCR p.Ala429Ser (c.1285G>T) is classified Likely benign in CALCR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-21). AlphaMissense: likely benign (0.1089); Rare (popmax 0.695%, afr).

How common is CALCR p.Ala429Ser (c.1285G>T) in the general population?

CALCR p.Ala429Ser (c.1285G>T) is rare (popmax 0.695%, afr) (gnomAD).

What do computational predictors say about CALCR p.Ala429Ser (c.1285G>T)?

AlphaMissense predicts likely benign (score 0.1089) — an in-silico prediction, not a clinical call.

CALCR p.Ala429Ser

c.1285G>T · rs150335791 · VCV731330

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1089 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.695%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1089	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -8.40	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 0.36	GERP -2.6, phastCons 0.001
Regional constraint	o/e 0.95	unconstrained · MANE · 61 kb · p 0.2 · regional, not allelic
Overall
CADD	0.284	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 0.695% African / African-American · 521/75,016 alleles

Filtering AF 0.645% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.626%

Overall 0.0369% 595/1,613,770 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.695%	144
Admixed American	0.0666%	1,501
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.04%	2,500
South Asian	0.0011%	91,064
European (non-Finnish)	0.000339%	294,931

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: CALCR
Protein: p.Ala429Ser
Coding: c.1285G>T
MANE Select: NM_001742
dbSNP: rs150335791
Type: single nucleotide variant
Location: chr7:93426496 (GRCh38)
Gene constraint: LOEUF 1.039 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.14 · 32 PDB

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

Similar variants

CALCR p.Val283Met Uncertain significance ★★ ⚠ same type
CALCR c.1149+72A>G Benign ★★ same type
CALCR c.1191+167C>A Benign ★★ same type
CALCR c.206-113T>G Benign ★★ same type
CALCR c.429+37T>C Benign ★★ same type
CALCR c.51+105C>T Benign ★★ same type
CALCR c.521+53C>T Benign ★★ same type
CALCR c.522-1226A>G Benign ★★ 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/calcr-p-ala429ser (accessed [today's date]).

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