Is SP7 p.Pro100Ser (c.298C>T) pathogenic?

SP7 p.Pro100Ser (c.298C>T) is classified Uncertain significance in SP7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-18). AlphaMissense: likely benign (0.0997); Very rare (popmax 0.00678%, nfe).

How common is SP7 p.Pro100Ser (c.298C>T) in the general population?

SP7 p.Pro100Ser (c.298C>T) is very rare (popmax 0.00678%, nfe) (gnomAD).

What do computational predictors say about SP7 p.Pro100Ser (c.298C>T)?

AlphaMissense predicts likely benign (score 0.0997) — an in-silico prediction, not a clinical call.

SP7 p.Pro100Ser

c.298C>T · rs370592247 · VCV1347155

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0997 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00678%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0997	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -6.39	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 6.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,497 bp · p 0.16 · regional, not allelic
Overall
CADD	18.05	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 0.00678% European (non-Finnish) · 80/1,179,882 alleles

Filtering AF 0.00555% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00533% 86/1,613,718 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00678%	14,749
Admixed American	0.005%	19,999
Remaining individualsnot grpmax-eligible	0.0032%	31,231
African / African-American	0.00134%	74,890

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: SP7
Protein: p.Pro100Ser
Coding: c.298C>T
MANE Select: NM_001173467
dbSNP: rs370592247
Type: single nucleotide variant
Location: chr12:53329144 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 52.78
Residue 100: the 'disordered' region

Full SP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SP7 p.Ala2Val Uncertain significance ★★ ⚠ same type
SP7 p.Arg267Cys Uncertain significance ★★ ⚠ same type
SP7 p.Arg280Leu Uncertain significance ★★ ⚠ same type
SP7 p.Arg280Trp Uncertain significance ★★ ⚠ same type
SP7 p.Arg316His Uncertain significance ★★ ⚠ same type
SP7 p.Arg350Trp Uncertain significance ★★ ⚠ same type
SP7 p.Arg362His Uncertain significance ★★ ⚠ same type
SP7 p.Arg365Ter 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/sp7-p-pro100ser (accessed [today's date]).

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