Is CD300LF p.Pro25Ser (c.73C>T) pathogenic?

CD300LF p.Pro25Ser (c.73C>T) is classified Uncertain significance in CD300LF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: ambiguous (0.4691); Very rare (popmax 0.00329%, sas).

How common is CD300LF p.Pro25Ser (c.73C>T) in the general population?

CD300LF p.Pro25Ser (c.73C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about CD300LF p.Pro25Ser (c.73C>T)?

AlphaMissense predicts ambiguous (score 0.4691) — an in-silico prediction, not a clinical call.

CD300LF p.Pro25Ser

c.73C>T · rs202161884 · VCV3140536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4691 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4691	ambiguous
REVEL	0.096	moderately benign-leaning
SaProt	LLR -11.44	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 3.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 18 kb · p 0.64 · regional, not allelic
Overall
CADD	21.6	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 0.00329% South Asian · 3/91,060 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00031% 5/1,613,572 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,353
Remaining individualsnot grpmax-eligible	0.0016%	62,464
African / African-American	0.00134%	74,894

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: CD300LF
Protein: p.Pro25Ser
Coding: c.73C>T
MANE Select: NM_139018
dbSNP: rs202161884
Type: single nucleotide variant
Location: chr17:74704787 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.16 · 1 PDB
Residue 25: the ig-like v-type domain

Full CD300LF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD300LF p.Ala103Val Uncertain significance ★ ⚠ same type
CD300LF p.Arg55Gln Uncertain significance ★ ⚠ same type
CD300LF p.Arg55Gly Uncertain significance ★ same type
CD300LF p.Arg79Gln Uncertain significance ★ ⚠ same type
CD300LF p.Arg79Pro Uncertain significance ★ ⚠ same type
CD300LF p.Arg79Trp Uncertain significance ★ ⚠ same type
CD300LF p.Arg89Cys Uncertain significance ★ ⚠ same type
CD300LF p.Asn88Thr 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/cd300lf-p-pro25ser (accessed [today's date]).

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