Is CD14 p.Ala114Thr (c.340G>A) pathogenic?

CD14 p.Ala114Thr (c.340G>A) is classified Uncertain significance in CD14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: likely benign (0.1188); Ultra-rare (popmax 0.0145%, nfe).

How common is CD14 p.Ala114Thr (c.340G>A) in the general population?

CD14 p.Ala114Thr (c.340G>A) is ultra-rare (popmax 0.0145%, nfe) (gnomAD).

What do computational predictors say about CD14 p.Ala114Thr (c.340G>A)?

AlphaMissense predicts likely benign (score 0.1188) — an in-silico prediction, not a clinical call.

CD14 p.Ala114Thr

c.340G>A · rs142233870 · VCV3140291

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1188 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0145%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1188	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -6.58	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 1.7	GERP 1.1, phastCons 0.013
Regional constraint	o/e 0.96	unconstrained · MANE · 1,212 bp · p 0.37 · regional, not allelic
Overall
CADD	18.16	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 0.0145% European (non-Finnish) · 171/1,180,036 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.012%

Overall 0.0112% 180/1,613,676 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0145%	6,901
Remaining individualsnot grpmax-eligible	0.0096%	10,414
African / African-American	0.004%	24,982

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.Ala114Thr
Coding: c.340G>A
MANE Select: NM_000591
dbSNP: rs142233870
Type: single nucleotide variant
Location: chr5:140632644 (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.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
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-ala114thr (accessed [today's date]).

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