Is CD300E p.Pro143Ser (c.427C>T) pathogenic?

CD300E p.Pro143Ser (c.427C>T) is classified Uncertain significance in CD300E (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: likely benign (0.0694); Very rare (popmax 0.008%, afr).

How common is CD300E p.Pro143Ser (c.427C>T) in the general population?

CD300E p.Pro143Ser (c.427C>T) is very rare (popmax 0.008%, afr) (gnomAD).

What do computational predictors say about CD300E p.Pro143Ser (c.427C>T)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

CD300E p.Pro143Ser

c.427C>T · VCV3829516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -5.88	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 -0.23	GERP -2.1
Regional constraint	o/e 0.93	unconstrained · MANE · 11 kb · p 0.29 · regional, not allelic
Overall
CADD	0.114	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 0.008% African / African-American · 6/75,034 alleles

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

Overall 0.000372% 6/1,614,062 alleles · very rare exomes 5/1,461,776 · genomes 1/152,286 · joint denominator

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.Pro143Ser
Coding: c.427C>T
MANE Select: NM_181449
Type: single nucleotide variant
Location: chr17:74613995 (GRCh38)
Gene constraint: LOEUF 1.05 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.04

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-pro143ser (accessed [today's date]).

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