Is ST7 p.Leu38Pro (c.113T>C) pathogenic?

ST7 p.Leu38Pro (c.113T>C) is classified Uncertain significance in ST7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely pathogenic (0.992); Very rare (popmax 0.00216%, nfe).

How common is ST7 p.Leu38Pro (c.113T>C) in the general population?

ST7 p.Leu38Pro (c.113T>C) is very rare (popmax 0.00216%, nfe) (gnomAD).

What do computational predictors say about ST7 p.Leu38Pro (c.113T>C)?

AlphaMissense predicts likely pathogenic (score 0.992) — an in-silico prediction, not a clinical call.

ST7 p.Leu38Pro

c.113T>C · VCV4175850

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00216%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.992	likely pathogenic
REVEL	0.305	indeterminate
SaProt	LLR -10.40	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 6.8	GERP 0.81, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 150 bp · p 0.22 · regional, not allelic
Overall
CADD	26.0	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 0.00216% European (non-Finnish) · 24/1,111,158 alleles

Filtering AF 0.00146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00167% 25/1,499,454 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00216%	46,298
Remaining individualsnot grpmax-eligible	0.00181%	55,238

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.Leu38Pro
Coding: c.113T>C
MANE Select: NM_001369598
Type: single nucleotide variant
Location: chr7:116953653 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 80.60

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

Similar variants

ST7 p.Leu38Gln Uncertain significance ★ ⚠ same residue
ST7 c.1638+860G>T Likely benign ★★ same type
ST7 c.1638+917G>T Likely benign ★★ same type
ST7 c.1638+799A>T Uncertain significance ★ ⚠ same type
ST7 c.1638+818C>T Uncertain significance ★ ⚠ same type
ST7 c.1638+859C>T Uncertain significance ★ ⚠ same type
ST7 c.1638+880A>G Uncertain significance ★ ⚠ same type
ST7 c.1638+887C>T 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/st7-p-leu38pro (accessed [today's date]).

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