Is CD300C p.Val127Ala (c.380T>C) pathogenic?

CD300C p.Val127Ala (c.380T>C) is classified Uncertain significance in CD300C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-04). AlphaMissense: ambiguous (0.4957); Ultra-rare (popmax 0.0133%, amr).

How common is CD300C p.Val127Ala (c.380T>C) in the general population?

CD300C p.Val127Ala (c.380T>C) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about CD300C p.Val127Ala (c.380T>C)?

AlphaMissense predicts ambiguous (score 0.4957) — an in-silico prediction, not a clinical call.

CD300C p.Val127Ala

c.380T>C · VCV3998188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4957 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4957	ambiguous
REVEL	0.134	moderately benign-leaning
SaProt	LLR -12.18	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.64 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP 0.93, phastCons 0.7
Regional constraint	o/e 0.96	unconstrained · MANE · 4,190 bp · p 0.54 · regional, not allelic
Overall
CADD	22.3	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

Grpmax group 0.0133% Admixed American · 8/59,972 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.00267% 43/1,612,108 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,496
African / African-American	0.00534%	18,709
European (non-Finnish)	0.00246%	40,638
East Asian	0.00223%	44,798
South Asian	0.0011%	91,040

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.Val127Ala
Coding: c.380T>C
MANE Select: NM_006678
Type: single nucleotide variant
Location: chr17:74544629 (GRCh38)
Gene constraint: LOEUF 1.043 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.06 · 1 PDB
Residue 127: 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-val127ala (accessed [today's date]).

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