Is ST14 p.Pro390= (c.1170C>T) pathogenic?

ST14 p.Pro390= (c.1170C>T) is classified Likely benign in ST14 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-11). Ultra-rare (popmax 0.0658%, nfe).

How common is ST14 p.Pro390= (c.1170C>T) in the general population?

ST14 p.Pro390= (c.1170C>T) is ultra-rare (popmax 0.0658%, nfe) (gnomAD).

ST14 p.Pro390=

c.1170C>T · rs148170078 · VCV2858510

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0658%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.12	GERP -1.7
Overall
CADD	11.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0658% European (non-Finnish) · 775/1,178,542 alleles

Filtering AF 0.0619% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0603%

Overall 0.0525% 845/1,609,998 alleles · ultra-rare exomes 792/1,457,726 · genomes 53/152,272 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0722%	1,385
European (non-Finnish)grpmax	0.0658%	1,521
African / African-American	0.02%	4,999
Middle Eastern	0.0166%	6,038
Admixed American	0.0101%	9,907
East Asian	0.00447%	22,362
South Asian	0.00111%	90,026

Remaining individuals 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.Pro390=
Coding: c.1170C>T
MANE Select: NM_021978
dbSNP: rs148170078
Type: single nucleotide variant
Location: chr11:130196395 (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 390: the cub 2 domain

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

Similar variants

ST14 p.Ala557Thr Uncertain significance ★★ ⚠ same type
ST14 p.Arg227Gly Uncertain significance ★★ ⚠ same type
ST14 p.Gly272Ser Uncertain significance ★★ ⚠ same type
ST14 p.Gly642Ser Uncertain significance ★★ ⚠ same type
ST14 p.Lys743Asn Uncertain significance ★★ ⚠ same type
ST14 p.Pro526Leu Uncertain significance ★★ ⚠ same type
ST14 p.Ser449Phe Uncertain significance ★★ ⚠ same type
ST14 p.Thr419Ala 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/st14-p-pro390 (accessed [today's date]).

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