Is SELL p.Pro189Ser (c.565C>T) pathogenic?

SELL p.Pro189Ser (c.565C>T) is classified Uncertain significance in SELL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.0901); Ultra-rare (popmax 0.0491%, eas).

How common is SELL p.Pro189Ser (c.565C>T) in the general population?

SELL p.Pro189Ser (c.565C>T) is ultra-rare (popmax 0.0491%, eas) (gnomAD).

What do computational predictors say about SELL p.Pro189Ser (c.565C>T)?

AlphaMissense predicts likely benign (score 0.0901) — an in-silico prediction, not a clinical call.

SELL p.Pro189Ser

c.565C>T · rs777439951 · VCV2263614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0901 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0491%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0901	likely benign
REVEL	0.351	indeterminate
SaProt	LLR -7.31	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.054, phastCons 0.48
Regional constraint	o/e 1.03	unconstrained · MANE · 20 kb · p 0.58 · regional, not allelic
Overall
CADD	18.5	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 0.0491% East Asian · 22/44,780 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.028%

Overall 0.00137% 22/1,611,322 alleles · ultra-rare exomes 20/1,459,278 · genomes 2/152,044 · joint denominator

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: SELL
Protein: p.Pro189Ser
Coding: c.565C>T
MANE Select: NM_000655
dbSNP: rs777439951
Type: single nucleotide variant
Location: chr1:169707357 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.76 · 3 PDB
Residue 189: a β-strand; the egf-like domain

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

Similar variants

SELL p.Glu201Gln Benign ★★ same type
SELL p.Gly117= Benign ★★ same type
SELL c.-17A>G Uncertain significance ★ same type
SELL p.Ala158Asp Uncertain significance ★ ⚠ same type
SELL p.Ala277Val Uncertain significance ★ ⚠ same type
SELL p.Arg357Ile Uncertain significance ★ ⚠ same type
SELL p.Arg84Cys Uncertain significance ★ ⚠ same type
SELL p.Asn113Ser 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/sell-p-pro189ser (accessed [today's date]).

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