Is CD14 p.Pro251Arg (c.752C>G) pathogenic?

CD14 p.Pro251Arg (c.752C>G) is classified Uncertain significance in CD14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: likely pathogenic (0.6715); Very rare (popmax 0.0011%, sas).

How common is CD14 p.Pro251Arg (c.752C>G) in the general population?

CD14 p.Pro251Arg (c.752C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CD14 p.Pro251Arg (c.752C>G)?

AlphaMissense predicts likely pathogenic (score 0.6715) — an in-silico prediction, not a clinical call.

CD14 p.Pro251Arg

c.752C>G · rs764093281 · VCV2325366

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6715 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6715	likely pathogenic
REVEL	0.21	benign-leaning
SaProt	LLR -14.79	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.94, phastCons 0.91
Regional constraint	o/e 0.96	unconstrained · MANE · 1,212 bp · p 0.37 · regional, not allelic
Overall
CADD	18.09	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 0.0011% South Asian · 1/91,082 alleles

Overall 0.000657% 1/152,242 alleles · very rare

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: CD14
Protein: p.Pro251Arg
Coding: c.752C>G
MANE Select: NM_000591
dbSNP: rs764093281
Type: single nucleotide variant
Location: chr5:140632232 (GRCh38)
Gene constraint: LOEUF 1.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.36 · 1 PDB
Residue 251: a disulfide bond

Full CD14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD14 p.Ala114Thr Uncertain significance ★ ⚠ same type
CD14 p.Ala143Gly Uncertain significance ★ ⚠ same type
CD14 p.Ala184Thr Uncertain significance ★ ⚠ same type
CD14 p.Ala269Thr Uncertain significance ★ ⚠ same type
CD14 p.Ala75Gly Uncertain significance ★ ⚠ same type
CD14 p.Ala98Ser Uncertain significance ★ ⚠ same type
CD14 p.Arg111His Uncertain significance ★ ⚠ same type
CD14 p.Arg117Ser 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/cd14-p-pro251arg (accessed [today's date]).

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