Is ST14 p.Val417= (c.1251C>T) pathogenic?

ST14 p.Val417= (c.1251C>T) is classified Likely benign in ST14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with ST14 p.Val417= (c.1251C>T)?

ST14 p.Val417= (c.1251C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ST14 p.Val417= (c.1251C>T) in the general population?

ST14 p.Val417= (c.1251C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

ST14 p.Val417=

c.1251C>T · VCV4175717

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.3	GERP -3.6
Overall
CADD	0.521	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.00155% 25/1,612,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0253%	3,956
Middle Easterngrpmax	0.0164%	6,080
African / African-American	0.00402%	24,895
European (non-Finnish)	0.000424%	235,882

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ST14
Protein: p.Val417=
Coding: c.1251C>T
MANE Select: NM_021978
Type: single nucleotide variant
Location: chr11:130196597 (GRCh38)
Gene constraint: LOEUF 0.589 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.23 · 25 PDB
Residue 417: the cub 2 domain

Full ST14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ST14 p.Val417Ile Uncertain significance ★ ⚠ same residue
ST14 p.Ala557Thr Uncertain significance ★★ ⚠ same condition
ST14 p.Arg227Gly Uncertain significance ★★ ⚠ same condition
ST14 p.Gly272Ser Uncertain significance ★★ ⚠ same condition
ST14 p.Gly642Ser Uncertain significance ★★ ⚠ same condition
ST14 p.Lys743Asn Uncertain significance ★★ ⚠ same condition
ST14 p.Pro526Leu Uncertain significance ★★ ⚠ same condition
ST14 p.Ser449Phe Uncertain significance ★★ ⚠ same condition

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/st14-p-val417 (accessed [today's date]).

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