Is CALCR p.Ser27= (c.81A>G) pathogenic?

CALCR p.Ser27= (c.81A>G) is classified Likely benign in CALCR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-01-03). Rare (popmax 0.239%, amr); Associated with CALCR-related disorder.

What condition is associated with CALCR p.Ser27= (c.81A>G)?

CALCR p.Ser27= (c.81A>G) is associated with CALCR-related disorder (ClinVar).

How common is CALCR p.Ser27= (c.81A>G) in the general population?

CALCR p.Ser27= (c.81A>G) is rare (popmax 0.239%, amr) (gnomAD).

CALCR p.Ser27=

c.81A>G · rs780870954 · VCV3035666

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.239%, amr)

Conditions

CALCR-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -2.7
Overall
CADD	0.728	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.239% Admixed American · 143/59,826 alleles

Filtering AF 0.207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.195%

Overall 0.00893% 144/1,612,318 alleles · rare exomes 139/1,460,478 · genomes 5/151,840 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.239%	418
Remaining individualsnot grpmax-eligible	0.0016%	62,390

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.Ser27=
Coding: c.81A>G
MANE Select: NM_001742
dbSNP: rs780870954
Type: single nucleotide variant
Location: chr7:93479478 (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

Disease context

CALCR-related disorder

Similar variants

CALCR p.Val283Met Uncertain significance ★★ ⚠ same condition
CALCR p.Leu176Phe Uncertain significance ★ ⚠ same condition
CALCR p.Glu457Lys Likely benign same condition
CALCR p.His331= Likely benign same condition
CALCR p.Ile160Val Likely benign same condition
CALCR p.Ser175Asn Benign same condition
CALCR c.1149+72A>G Benign ★★ same type
CALCR c.1191+167C>A 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-ser27 (accessed [today's date]).

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