Is CCL14 p.Phe37Leu (c.109T>C) pathogenic?

CCL14 p.Phe37Leu (c.109T>C) is classified Likely benign in CCL14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-23). AlphaMissense: likely pathogenic (0.8321); Very rare (popmax 0.000424%, nfe).

How common is CCL14 p.Phe37Leu (c.109T>C) in the general population?

CCL14 p.Phe37Leu (c.109T>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about CCL14 p.Phe37Leu (c.109T>C)?

AlphaMissense predicts likely pathogenic (score 0.8321) — an in-silico prediction, not a clinical call.

CCL14 p.Phe37Leu

c.109T>C · VCV4649922

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8321 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8321	likely pathogenic · top 7% in CCL14
REVEL	0.04	moderately benign-leaning
SaProt	LLR -8.10	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2
Regional constraint	o/e 1.07	unconstrained · MANE · 2,845 bp · p 0.42 · regional, not allelic
Overall
CADD	2.561	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 0.000424% European (non-Finnish) · 5/1,179,874 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,392 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: CCL14
Protein: p.Phe37Leu
Coding: c.109T>C
MANE Select: NM_032963
Type: single nucleotide variant
Location: chr17:35984423 (GRCh38)
Gene constraint: LOEUF 1.642 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 86.15 · 2 PDB
Residue 37: a disulfide bond

Full CCL14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SCYL2 p.His37Pro Uncertain significance ★ ⚠ same residue
SCYL2 p.Leu478Pro Uncertain significance ★★ ⚠ same type
SCYL2 p.Met321Val Uncertain significance ★★ ⚠ same type
SCYL2 c.1096-23T>A Benign ★★ same type
SCYL2 c.177+35C>A Benign ★★ same type
SCYL2 p.Ile615Met Likely benign ★★ same type
SCYL2 p.Leu723= Benign ★★ same type
SCYL2 p.Arg100Ter Pathogenic ★ 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/ccl14-p-phe37leu (accessed [today's date]).

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