Is CD14 p.Arg117Ser (c.349C>A) pathogenic?

CD14 p.Arg117Ser (c.349C>A) is classified Uncertain significance in CD14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: ambiguous (0.5074); Very rare (popmax 0.000508%, nfe).

How common is CD14 p.Arg117Ser (c.349C>A) in the general population?

CD14 p.Arg117Ser (c.349C>A) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about CD14 p.Arg117Ser (c.349C>A)?

AlphaMissense predicts ambiguous (score 0.5074) — an in-silico prediction, not a clinical call.

CD14 p.Arg117Ser

c.349C>A · VCV4222543

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5074 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5074	ambiguous
REVEL	0.126	moderately benign-leaning
SaProt	LLR -5.83	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,212 bp · p 0.37 · regional, not allelic
Overall
CADD	25.0	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 0.000508% European (non-Finnish) · 6/1,180,032 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000411% 6/1,461,510 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.Arg117Ser
Coding: c.349C>A
MANE Select: NM_000591
Type: single nucleotide variant
Location: chr5:140632635 (GRCh38)
Gene constraint: LOEUF 1.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.36 · 1 PDB

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.Arg158Cys 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-arg117ser (accessed [today's date]).

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