Is CLEC17A p.Leu155Phe (c.463C>T) pathogenic?

CLEC17A p.Leu155Phe (c.463C>T) is classified Uncertain significance in CLEC17A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-10). AlphaMissense: likely benign (0.1649); Very rare (popmax 0.00334%, sas).

How common is CLEC17A p.Leu155Phe (c.463C>T) in the general population?

CLEC17A p.Leu155Phe (c.463C>T) is very rare (popmax 0.00334%, sas) (gnomAD).

What do computational predictors say about CLEC17A p.Leu155Phe (c.463C>T)?

AlphaMissense predicts likely benign (score 0.1649) — an in-silico prediction, not a clinical call.

CLEC17A p.Leu155Phe

c.463C>T · VCV4654251

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1649 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1649	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.88	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 -0.17	GERP -0.71, phastCons 0.001
Regional constraint	o/e 0.90	unconstrained · MANE · 27 kb · p 0.03 · regional, not allelic
Overall
CADD	3.658	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 0.00334% South Asian · 3/89,816 alleles

Filtering AF 0.000887% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000446%

Overall 0.000684% 11/1,608,920 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00334%	29,939
Remaining individualsnot grpmax-eligible	0.00161%	62,266
European (non-Finnish)	0.000594%	168,251

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: CLEC17A
Protein: p.Leu155Phe
Coding: c.463C>T
MANE Select: NM_001204118
Type: single nucleotide variant
Location: chr19:14596893 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.08

Full CLEC17A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC17A p.Arg158Met Uncertain significance ★ ⚠ same type
CLEC17A p.Arg250Cys Uncertain significance ★ ⚠ same type
CLEC17A p.Arg250His Uncertain significance ★ ⚠ same type
CLEC17A p.Arg250Pro Uncertain significance ★ ⚠ same type
CLEC17A p.Asn137Lys Uncertain significance ★ ⚠ same type
CLEC17A p.Asn3Asp Uncertain significance ★ ⚠ same type
CLEC17A p.Asp123Gly Uncertain significance ★ ⚠ same type
CLEC17A p.Asp228Asn 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/clec17a-p-leu155phe (accessed [today's date]).

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