Is SCLY p.Ser210Arg (c.628A>C) pathogenic?

SCLY p.Ser210Arg (c.628A>C) is classified Uncertain significance in SCLY (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely pathogenic (0.841); Absent from gnomAD v4.1.

How common is SCLY p.Ser210Arg (c.628A>C) in the general population?

SCLY p.Ser210Arg (c.628A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SCLY p.Ser210Arg (c.628A>C)?

AlphaMissense predicts likely pathogenic (score 0.841) — an in-silico prediction, not a clinical call.

SCLY p.Ser210Arg

c.628A>C · rs774661539 · VCV2557971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.841 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.841	likely pathogenic
REVEL	0.319	indeterminate
SaProt	LLR -12.47	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.4	GERP 0.77, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 37 kb · p 0.42 · regional, not allelic
Overall
CADD	21.6	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

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: SCLY
Protein: p.Ser210Arg
Coding: c.628A>C
MANE Select: NM_016510
dbSNP: rs774661539
Type: single nucleotide variant
Location: chr2:238082060 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.14 · 2 PDB
Residue 210: an α-helix

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

Similar variants

SCLY c.612+7C>T Benign ★★ same type
SCLY p.Ile86Met Benign ★★ same type
SCLY p.Phe276Ser Benign ★★ same type
SCLY p.Val326Ile Benign ★★ same type
SCLY p.Ala161Gly Uncertain significance ★ ⚠ same type
SCLY p.Ala183Val Uncertain significance ★ ⚠ same type
SCLY p.Ala235Ser Uncertain significance ★ ⚠ same type
SCLY p.Ala267Thr 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/scly-p-ser210arg (accessed [today's date]).

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