Is SRPX2 p.Ser315Pro (c.943T>C) pathogenic?

SRPX2 p.Ser315Pro (c.943T>C) is classified Uncertain significance in SRPX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-12-14). AlphaMissense: likely benign (0.1173); Very rare (popmax 0.00219%, amr).

How common is SRPX2 p.Ser315Pro (c.943T>C) in the general population?

SRPX2 p.Ser315Pro (c.943T>C) is very rare (popmax 0.00219%, amr) (gnomAD).

What do computational predictors say about SRPX2 p.Ser315Pro (c.943T>C)?

AlphaMissense predicts likely benign (score 0.1173) — an in-silico prediction, not a clinical call.

SRPX2 p.Ser315Pro

c.943T>C · rs796053344 · VCV207394

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1173 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00219%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1173	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.94 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.3	GERP 0.83, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 25 kb · p 0.025 · regional, not allelic
Overall
CADD	17.19	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 0.00219% Admixed American · 1/45,682 alleles

Overall 8.28e-05% 1/1,208,292 alleles · very rare exomes 0/1,096,045 · genomes 1/112,247 · joint denominator

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: SRPX2
Protein: p.Ser315Pro
Coding: c.943T>C
MANE Select: NM_014467
dbSNP: rs796053344
Type: single nucleotide variant
Location: chrX:100666915 (GRCh38)
Structure: AlphaFold pLDDT 86.75
Residue 315: the sushi 3 domain

Full SRPX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SRPX2 c.961+1G>A Uncertain significance ★★ same type
SRPX2 p.Ala201Val Uncertain significance ★★ ⚠ same type
SRPX2 p.Arg185Cys Uncertain significance ★★ ⚠ same type
SRPX2 p.Arg185Leu Uncertain significance ★★ ⚠ same type
SRPX2 p.Arg413His Uncertain significance ★★ ⚠ same type
SRPX2 p.Arg430His Uncertain significance ★★ ⚠ same type
SRPX2 p.Arg54Gln Uncertain significance ★★ ⚠ same type
SRPX2 p.Asn327Lys 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/srpx2-p-ser315pro (accessed [today's date]).

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