Is CD300E p.Val76Met (c.226G>A) pathogenic?

CD300E p.Val76Met (c.226G>A) is classified Uncertain significance in CD300E (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). AlphaMissense: ambiguous (0.3468); Very rare (popmax 0.00223%, eas).

How common is CD300E p.Val76Met (c.226G>A) in the general population?

CD300E p.Val76Met (c.226G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CD300E p.Val76Met (c.226G>A)?

AlphaMissense predicts ambiguous (score 0.3468) — an in-silico prediction, not a clinical call.

CD300E p.Val76Met

c.226G>A · VCV3488031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3468 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3468	ambiguous
REVEL	0.124	moderately benign-leaning
SaProt	LLR -10.44	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.22	GERP 2, phastCons 0.011
Regional constraint	o/e 0.93	unconstrained · MANE · 11 kb · p 0.29 · regional, not allelic
Overall
CADD	21.0	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 0.00223% East Asian · 1/44,896 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00124% 20/1,614,100 alleles · very rare exomes 15/1,461,890 · genomes 5/152,210 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,896
European (non-Finnish)	0.00153%	65,558
African / African-American	0.00133%	74,940

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: CD300E
Protein: p.Val76Met
Coding: c.226G>A
MANE Select: NM_181449
Type: single nucleotide variant
Location: chr17:74617280 (GRCh38)
Gene constraint: LOEUF 1.05 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.04
Residue 76: the ig-like v-type domain

Full CD300E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD300E p.Ala130Glu Uncertain significance ★ ⚠ same type
CD300E p.Ala99Thr Uncertain significance ★ ⚠ same type
CD300E p.Arg168Gln Uncertain significance ★ ⚠ same type
CD300E p.Arg51Leu Uncertain significance ★ same type
CD300E p.Asn150Lys Uncertain significance ★ ⚠ same type
CD300E p.Cys50Arg Uncertain significance ★ ⚠ same type
CD300E p.Glu39Lys Uncertain significance ★ ⚠ same type
CD300E p.Leu16Phe 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/cd300e-p-val76met (accessed [today's date]).

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