Is CD300C p.Phe93Leu (c.277T>C) pathogenic?

CD300C p.Phe93Leu (c.277T>C) is classified Uncertain significance in CD300C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-17). AlphaMissense: likely pathogenic (0.9588); Ultra-rare (popmax 0.013%, nfe).

How common is CD300C p.Phe93Leu (c.277T>C) in the general population?

CD300C p.Phe93Leu (c.277T>C) is ultra-rare (popmax 0.013%, nfe) (gnomAD).

What do computational predictors say about CD300C p.Phe93Leu (c.277T>C)?

AlphaMissense predicts likely pathogenic (score 0.9588) — an in-silico prediction, not a clinical call.

CD300C p.Phe93Leu

c.277T>C · rs368005305 · VCV2401164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9588 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.013%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9588	likely pathogenic · top 1% in CD300C
REVEL	0.431	indeterminate
SaProt	LLR -13.03	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.91, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 4,190 bp · p 0.54 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.013% European (non-Finnish) · 153/1,180,052 alleles

Filtering AF 0.0113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.01% 162/1,614,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.013%	7,713
Remaining individualsnot grpmax-eligible	0.0112%	8,927
African / African-American	0.00267%	37,475

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.Phe93Leu
Coding: c.277T>C
MANE Select: NM_006678
dbSNP: rs368005305
Type: single nucleotide variant
Location: chr17:74544732 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.06 · 1 PDB
Residue 93: 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.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-phe93leu (accessed [today's date]).

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