Is SELP p.Ser557Pro (c.1669T>C) pathogenic?

SELP p.Ser557Pro (c.1669T>C) is classified Uncertain significance in SELP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.1695); Absent from gnomAD v4.1.

How common is SELP p.Ser557Pro (c.1669T>C) in the general population?

SELP p.Ser557Pro (c.1669T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SELP p.Ser557Pro (c.1669T>C)?

AlphaMissense predicts likely benign (score 0.1695) — an in-silico prediction, not a clinical call.

SELP p.Ser557Pro

c.1669T>C · VCV3952042

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1695 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1695	likely benign
REVEL	0.366	indeterminate
SaProt	LLR -15.00	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2	GERP 0.93, phastCons 0.57
Regional constraint	o/e 1.00	unconstrained · MANE · 40 kb · p 0.88 · regional, not allelic
Overall
CADD	15.59	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: SELP
Protein: p.Ser557Pro
Coding: c.1669T>C
MANE Select: NM_003005
Type: single nucleotide variant
Location: chr1:169603062 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.27 · 5 PDB
Residue 557: the sushi 6 domain

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

Similar variants

SELP p.Asn128= Benign ★★ same type
SELP p.Asn673Ser Benign ★★ same type
SELP p.Ser619Ala Benign ★★ same type
SELP p.Thr274Ile Benign ★★ same type
SELP p.Thr767= Benign ★★ same type
SELP p.Ala246Val Uncertain significance ★ ⚠ same type
SELP p.Ala329Thr Uncertain significance ★ ⚠ same type
SELP p.Ala405Gly 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/selp-p-ser557pro (accessed [today's date]).

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