Is SPRED1 p.Ser2Arg (c.6C>G) pathogenic?

SPRED1 p.Ser2Arg (c.6C>G) is classified Uncertain significance in SPRED1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-27). AlphaMissense: likely pathogenic (0.7978); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with SPRED1 p.Ser2Arg (c.6C>G)?

SPRED1 p.Ser2Arg (c.6C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is SPRED1 p.Ser2Arg (c.6C>G) in the general population?

SPRED1 p.Ser2Arg (c.6C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SPRED1 p.Ser2Arg (c.6C>G)?

AlphaMissense predicts likely pathogenic (score 0.7978) — an in-silico prediction, not a clinical call.

SPRED1 p.Ser2Arg

c.6C>G · VCV3448771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.7978	likely pathogenic
REVEL	0.362	indeterminate
SaProt	LLR -8.82	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Pangolin	Δ0.20	loss · gain 0.09 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 5.7	GERP 0.68, phastCons 1
Regional constraint	o/e 1.32	unconstrained · MANE · 46 kb · p 0.11 · regional, not allelic
Overall
CADD	27.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SPRED1
Protein: p.Ser2Arg
Coding: c.6C>G
MANE Select: NM_152594
Type: single nucleotide variant
Location: chr15:38253191 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.98 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.67 · 3 PDB
Residue 2: a modified residue (n-acetylserine)

Full SPRED1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPRED1 p.Arg16Ter Pathogenic ★★ same condition
SPRED1 p.Ala137Val Uncertain significance ★★ ⚠ same condition
SPRED1 p.Ala183Thr Uncertain significance ★★ ⚠ same condition
SPRED1 p.Ala19Gly Uncertain significance ★★ ⚠ same condition
SPRED1 p.Ala406Val Uncertain significance ★★ ⚠ same condition
SPRED1 p.Arg118Lys Uncertain significance ★★ ⚠ same condition
SPRED1 p.Arg16Gln Uncertain significance ★★ same condition
SPRED1 p.Arg214Trp Uncertain significance ★★ ⚠ same condition

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/spred1-p-ser2arg (accessed [today's date]).

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