Is CD300E p.Ala28Val (c.83C>T) pathogenic?

CD300E p.Ala28Val (c.83C>T) is classified Likely benign in CD300E (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-06). AlphaMissense: likely benign (0.0772); Very rare (popmax 0.00593%, nfe).

How common is CD300E p.Ala28Val (c.83C>T) in the general population?

CD300E p.Ala28Val (c.83C>T) is very rare (popmax 0.00593%, nfe) (gnomAD).

What do computational predictors say about CD300E p.Ala28Val (c.83C>T)?

AlphaMissense predicts likely benign (score 0.0772) — an in-silico prediction, not a clinical call.

CD300E p.Ala28Val

c.83C>T · rs139411937 · VCV2462629

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0772 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00593%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0772	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP -13	GERP -3.9
Regional constraint	o/e 0.93	unconstrained · MANE · 11 kb · p 0.29 · regional, not allelic
Overall
CADD	0.001	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 0.00593% European (non-Finnish) · 70/1,180,002 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.00527% 85/1,613,830 alleles · very rare exomes 82/1,461,644 · genomes 3/152,186 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.008%	12,498
European (non-Finnish)grpmax	0.00593%	16,857
East Asian	0.00446%	22,440
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
South Asian	0.00329%	30,357
African / African-American	0.00267%	37,502
Admixed American	0.00167%	59,994
Finnishnot grpmax-eligible	0.00157%	63,810

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala28Val
Coding: c.83C>T
MANE Select: NM_181449
dbSNP: rs139411937
Type: single nucleotide variant
Location: chr17:74617423 (GRCh38)
Gene constraint: LOEUF 1.05 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.04
Residue 28: 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-ala28val (accessed [today's date]).

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