Is ADAMTS14 p.Pro813Ser (c.2437C>T) pathogenic?

ADAMTS14 p.Pro813Ser (c.2437C>T) is classified Uncertain significance in ADAMTS14 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-14). AlphaMissense: likely benign (0.0631); Very rare (popmax 0.00936%, afr).

How common is ADAMTS14 p.Pro813Ser (c.2437C>T) in the general population?

ADAMTS14 p.Pro813Ser (c.2437C>T) is very rare (popmax 0.00936%, afr) (gnomAD).

What do computational predictors say about ADAMTS14 p.Pro813Ser (c.2437C>T)?

AlphaMissense predicts likely benign (score 0.0631) — an in-silico prediction, not a clinical call.

ADAMTS14 p.Pro813Ser

c.2437C>T · rs528095489 · VCV2611811

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0631 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00936%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0631	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -5.61	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 0.38	GERP -0.24
Regional constraint	o/e 0.94	unconstrained · MANE · 88 kb · p 0.018 · regional, not allelic
Overall
CADD	8.499	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 0.00936% African / African-American · 7/74,798 alleles

Filtering AF 0.00652% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00604%

Overall 0.00654% 105/1,604,982 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00936%	10,685
European (non-Finnish)	0.00785%	12,745
Remaining individualsnot grpmax-eligible	0.00484%	20,660
Admixed American	0.00334%	29,937
Finnishnot grpmax-eligible	0.00157%	63,896

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: ADAMTS14
Protein: p.Pro813Ser
Coding: c.2437C>T
MANE Select: NM_080722
dbSNP: rs528095489
Type: single nucleotide variant
Location: chr10:70751487 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.22
Residue 813: the 'spacer' region

Full ADAMTS14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAMTS14 p.Pro813Ala Uncertain significance ★ ⚠ same residue
ADAMTS14 p.Pro813Arg Uncertain significance ★ ⚠ same residue
ADAMTS14 p.Pro813Gln Uncertain significance ★ ⚠ same residue
ADAMTS14 p.Pro813Thr Uncertain significance ★ ⚠ same residue
ADAMTS14 p.Gly532Ser Uncertain significance ★★ ⚠ same type
ADAMTS14 c.870+3G>A Benign ★★ same type
ADAMTS14 p.Asp172= Benign ★★ same type
ADAMTS14 p.Glu1049Gly Benign ★★ 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/adamts14-p-pro813ser (accessed [today's date]).

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