Is CLEC17A p.Trp258Ser (c.773G>C) pathogenic?

CLEC17A p.Trp258Ser (c.773G>C) is classified Uncertain significance in CLEC17A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely pathogenic (0.9443); Very rare (popmax 0.0011%, sas).

How common is CLEC17A p.Trp258Ser (c.773G>C) in the general population?

CLEC17A p.Trp258Ser (c.773G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CLEC17A p.Trp258Ser (c.773G>C)?

AlphaMissense predicts likely pathogenic (score 0.9443) — an in-silico prediction, not a clinical call.

CLEC17A p.Trp258Ser

c.773G>C · rs751538925 · VCV3145609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9443 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9443	likely pathogenic · top 7% in CLEC17A
REVEL	0.472	indeterminate
SaProt	LLR -11.71	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 27 kb · p 0.03 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0011% South Asian · 1/91,088 alleles

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

Overall 0.000479% 7/1,461,698 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,088
European (non-Finnish)	0.000509%	196,650

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.Trp258Ser
Coding: c.773G>C
MANE Select: NM_001204118
dbSNP: rs751538925
Type: single nucleotide variant
Location: chr19:14600061 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.08
Residue 258: a disulfide bond

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-trp258ser (accessed [today's date]).

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