Is CD300C p.Arg44Pro (c.131G>C) pathogenic?

CD300C p.Arg44Pro (c.131G>C) is classified Uncertain significance in CD300C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely benign (0.2121); Very rare (popmax 0.00271%, nfe).

How common is CD300C p.Arg44Pro (c.131G>C) in the general population?

CD300C p.Arg44Pro (c.131G>C) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about CD300C p.Arg44Pro (c.131G>C)?

AlphaMissense predicts likely benign (score 0.2121) — an in-silico prediction, not a clinical call.

CD300C p.Arg44Pro

c.131G>C · VCV4650571

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2121 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2121	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -4.39	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 -20	GERP -3.9
Regional constraint	o/e 0.96	unconstrained · MANE · 4,190 bp · p 0.54 · regional, not allelic
Overall
CADD	0.005	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 0.00271% European (non-Finnish) · 32/1,179,996 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00198% 32/1,614,010 alleles · very rare

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: CD300C
Protein: p.Arg44Pro
Coding: c.131G>C
MANE Select: NM_006678
Type: single nucleotide variant
Location: chr17:74544878 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.06 · 1 PDB
Residue 44: a disulfide bond; the ig-like v-type domain

Full CD300C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD300C p.Arg44His Uncertain significance ★ ⚠ same residue
CD300C p.Ala13Gly Uncertain significance ★ ⚠ same type
CD300C p.Ala89Thr Uncertain significance ★ ⚠ same type
CD300C p.Ala89Val Uncertain significance ★ ⚠ same type
CD300C p.Arg210Ser Uncertain significance ★ ⚠ same type
CD300C p.Glu126Lys Uncertain significance ★ ⚠ same type
CD300C p.Glu170Lys Uncertain significance ★ ⚠ same type
CD300C p.Glu98Asp 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/cd300c-p-arg44pro (accessed [today's date]).

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