Is CALML5 p.Arg105Pro (c.314G>C) pathogenic?

CALML5 p.Arg105Pro (c.314G>C) is classified Uncertain significance in CALML5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely pathogenic (0.8103); Absent from gnomAD v4.1.

How common is CALML5 p.Arg105Pro (c.314G>C) in the general population?

CALML5 p.Arg105Pro (c.314G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CALML5 p.Arg105Pro (c.314G>C)?

AlphaMissense predicts likely pathogenic (score 0.8103) — an in-silico prediction, not a clinical call.

CALML5 p.Arg105Pro

c.314G>C · rs867744149 · VCV2237038

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8103 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8103	likely pathogenic
REVEL	0.213	benign-leaning
SaProt	LLR -12.22	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -2.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 437 bp · p 0.98 · regional, not allelic
Overall
CADD	21.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CALML5
Protein: p.Arg105Pro
Coding: c.314G>C
MANE Select: NM_017422
dbSNP: rs867744149
Type: single nucleotide variant
Location: chr10:5499125 (GRCh38)
Gene constraint: LOEUF 1.883 · pLI 0.30 (gnomAD)
Structure: AlphaFold pLDDT 81.24 · 1 PDB
Residue 105: an α-helix; the ef-hand 3 domain

Full CALML5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CALML5 p.Ala106Gly Uncertain significance ★ ⚠ same type
CALML5 p.Ala16Thr Uncertain significance ★ ⚠ same type
CALML5 p.Ala47Thr Uncertain significance ★ ⚠ same type
CALML5 p.Ala89Gly Uncertain significance ★ ⚠ same type
CALML5 p.Arg133Leu Uncertain significance ★ ⚠ same type
CALML5 p.Arg133Trp Uncertain significance ★ ⚠ same type
CALML5 p.Asp23Glu Uncertain significance ★ ⚠ same type
CALML5 p.Asp59Ala 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/calml5-p-arg105pro (accessed [today's date]).

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