Is CCL25 p.Tyr49Phe (c.146A>T) pathogenic?

CCL25 p.Tyr49Phe (c.146A>T) is classified Uncertain significance in CCL25 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: ambiguous (0.3572); Absent from gnomAD v4.1.

How common is CCL25 p.Tyr49Phe (c.146A>T) in the general population?

CCL25 p.Tyr49Phe (c.146A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCL25 p.Tyr49Phe (c.146A>T)?

AlphaMissense predicts ambiguous (score 0.3572) — an in-silico prediction, not a clinical call.

CCL25 p.Tyr49Phe

c.146A>T · rs2512471814 · VCV3139738

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3572 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3572	ambiguous
REVEL	0.104	moderately benign-leaning
SaProt	LLR -11.55	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 3.5	GERP -2.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 9,172 bp · p 0.025 · regional, not allelic
Overall
CADD	16.69	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCL25
Protein: p.Tyr49Phe
Coding: c.146A>T
MANE Select: NM_005624
dbSNP: rs2512471814
Type: single nucleotide variant
Location: chr19:8056224 (GRCh38)
Gene constraint: LOEUF 1.561 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.44
Residue 49: a disulfide bond

Full CCL25 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL25 p.Arg44Trp Benign ★★ ⚠ same type
CCL25 p.Ala18Val Uncertain significance ★ ⚠ same type
CCL25 p.Arg44Gln Uncertain significance ★ ⚠ same type
CCL25 p.Arg50Gln Uncertain significance ★ ⚠ same type
CCL25 p.Asn103Ser Uncertain significance ★ ⚠ same type
CCL25 p.Ile38Thr Uncertain significance ★ ⚠ same type
CCL25 p.Ile38Val Uncertain significance ★ ⚠ same type
CCL25 p.Phe97Leu 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/ccl25-p-tyr49phe (accessed [today's date]).

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