Is ST7 p.Ala4Val (c.11C>T) pathogenic?

ST7 p.Ala4Val (c.11C>T) is classified Uncertain significance in ST7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). AlphaMissense: likely benign (0.1037); Ultra-rare (popmax 0.0227%, amr).

How common is ST7 p.Ala4Val (c.11C>T) in the general population?

ST7 p.Ala4Val (c.11C>T) is ultra-rare (popmax 0.0227%, amr) (gnomAD).

What do computational predictors say about ST7 p.Ala4Val (c.11C>T)?

AlphaMissense predicts likely benign (score 0.1037) — an in-silico prediction, not a clinical call.

ST7 p.Ala4Val

c.11C>T · rs770090404 · VCV2352248

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1037 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1037	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -6.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.098, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 150 bp · p 0.22 · regional, not allelic
Overall
CADD	16.88	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 0.0227% Admixed American · 11/48,484 alleles

Filtering AF 0.0126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00975%

Overall 0.00304% 43/1,412,186 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0227%	4,408
Middle Eastern	0.0191%	5,238
Remaining individualsnot grpmax-eligible	0.0079%	12,653
European (non-Finnish)	0.00245%	40,801
African / African-American	0.00148%	67,498

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.Ala4Val
Coding: c.11C>T
MANE Select: NM_001369598
dbSNP: rs770090404
Type: single nucleotide variant
Location: chr7:116953551 (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 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
ST7 p.Ala188Gly 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-ala4val (accessed [today's date]).

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