Is SP7 p.Ala23Val (c.68C>T) pathogenic?

SP7 p.Ala23Val (c.68C>T) is classified Likely benign in SP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). AlphaMissense: ambiguous (0.3594); Rare (popmax 0.455%, eas).

How common is SP7 p.Ala23Val (c.68C>T) in the general population?

SP7 p.Ala23Val (c.68C>T) is rare (popmax 0.455%, eas) (gnomAD).

What do computational predictors say about SP7 p.Ala23Val (c.68C>T)?

AlphaMissense predicts ambiguous (score 0.3594) — an in-silico prediction, not a clinical call.

SP7 p.Ala23Val

c.68C>T · rs188929035 · VCV731363

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3594 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.455%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3594	ambiguous
REVEL	0.129	moderately benign-leaning
SaProt	LLR -8.44	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,497 bp · p 0.16 · regional, not allelic
Overall
CADD	25.3	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 0.455% East Asian · 204/44,884 alleles

Filtering AF 0.403% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.384%

Overall 0.0219% 354/1,613,968 alleles · rare exomes 317/1,461,694 · genomes 37/152,274 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.455%	220
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.016%	6,249
South Asian	0.0143%	7,006
European (non-Finnish)	0.0105%	9,515
Admixed American	0.00333%	30,008

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.Ala23Val
Coding: c.68C>T
MANE Select: NM_001173467
dbSNP: rs188929035
Type: single nucleotide variant
Location: chr12:53329374 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 52.78

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

Similar variants

SP7 p.Ala23= Uncertain significance ★ same residue
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

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-ala23val (accessed [today's date]).

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