Is CD300C p.Pro115Leu (c.344C>T) pathogenic?

CD300C p.Pro115Leu (c.344C>T) is classified Uncertain significance in CD300C (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). AlphaMissense: likely benign (0.1935); Very rare (popmax 0.00801%, afr).

How common is CD300C p.Pro115Leu (c.344C>T) in the general population?

CD300C p.Pro115Leu (c.344C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about CD300C p.Pro115Leu (c.344C>T)?

AlphaMissense predicts likely benign (score 0.1935) — an in-silico prediction, not a clinical call.

CD300C p.Pro115Leu

c.344C>T · rs374234481 · VCV2246420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1935 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1935	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -5.83	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 -8.2	GERP -3.6
Regional constraint	o/e 0.96	unconstrained · MANE · 4,190 bp · p 0.54 · regional, not allelic
Overall
CADD	1.226	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 0.00801% African / African-American · 6/74,950 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000867% 14/1,614,026 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,492
South Asian	0.00549%	18,216
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	8.47e-05%	1,180,008

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.Pro115Leu
Coding: c.344C>T
MANE Select: NM_006678
dbSNP: rs374234481
Type: single nucleotide variant
Location: chr17:74544665 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.06 · 1 PDB
Residue 115: the ig-like v-type domain

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

Similar variants

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.Arg44His Uncertain significance ★ ⚠ same type
CD300C p.Arg44Pro Uncertain significance ★ ⚠ same type
CD300C p.Glu126Lys Uncertain significance ★ ⚠ same type
CD300C p.Glu170Lys 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-pro115leu (accessed [today's date]).

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