Is ST7 p.Ser49Arg (c.145A>C) pathogenic?

ST7 p.Ser49Arg (c.145A>C) is classified Uncertain significance in ST7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely pathogenic (0.6535); Very rare (popmax 0.000453%, nfe).

How common is ST7 p.Ser49Arg (c.145A>C) in the general population?

ST7 p.Ser49Arg (c.145A>C) is very rare (popmax 0.000453%, nfe) (gnomAD).

What do computational predictors say about ST7 p.Ser49Arg (c.145A>C)?

AlphaMissense predicts likely pathogenic (score 0.6535) — an in-silico prediction, not a clinical call.

ST7 p.Ser49Arg

c.145A>C · rs1361699852 · VCV3170706

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6535 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000453%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6535	likely pathogenic
REVEL	0.041	moderately benign-leaning
SaProt	LLR -5.09	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.7	GERP 0.81, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 150 bp · p 0.22 · regional, not allelic
Overall
CADD	22.8	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

Grpmax group 0.000453% European (non-Finnish) · 5/1,103,924 alleles

Filtering AF 0.000133% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.6e-05%

Overall 0.000373% 5/1,338,876 alleles · very rare

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: ST7
Protein: p.Ser49Arg
Coding: c.145A>C
dbSNP: rs1361699852
Type: single nucleotide variant
Location: chr7:116953685 (GRCh38)

Full ST7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/st7-p-ser49arg (accessed [today's date]).

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