Is SP7 p.Ser80Arg (c.238A>C) pathogenic?

SP7 p.Ser80Arg (c.238A>C) is classified Uncertain significance in SP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). AlphaMissense: likely pathogenic (0.7318); Very rare (popmax 0.00729%, nfe).

How common is SP7 p.Ser80Arg (c.238A>C) in the general population?

SP7 p.Ser80Arg (c.238A>C) is very rare (popmax 0.00729%, nfe) (gnomAD).

What do computational predictors say about SP7 p.Ser80Arg (c.238A>C)?

AlphaMissense predicts likely pathogenic (score 0.7318) — an in-silico prediction, not a clinical call.

SP7 p.Ser80Arg

c.238A>C · rs748756178 · VCV2466042

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7318 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00729%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7318	likely pathogenic
REVEL	0.113	moderately benign-leaning
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,497 bp · p 0.16 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00729% European (non-Finnish) · 86/1,179,866 alleles

Filtering AF 0.00604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00558% 90/1,613,662 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00729%	13,719
Remaining individualsnot grpmax-eligible	0.0064%	15,615

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.Ser80Arg
Coding: c.238A>C
MANE Select: NM_001173467
dbSNP: rs748756178
Type: single nucleotide variant
Location: chr12:53329204 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 52.78
Residue 80: 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-ser80arg (accessed [today's date]).

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