Is SP9 p.Ser448Phe (c.1343C>T) pathogenic?

SP9 p.Ser448Phe (c.1343C>T) is classified Uncertain significance in SP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-20). AlphaMissense: likely pathogenic (0.6144); Absent from gnomAD v4.1.

How common is SP9 p.Ser448Phe (c.1343C>T) in the general population?

SP9 p.Ser448Phe (c.1343C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SP9 p.Ser448Phe (c.1343C>T)?

AlphaMissense predicts likely pathogenic (score 0.6144) — an in-silico prediction, not a clinical call.

SP9 p.Ser448Phe

c.1343C>T · rs981960411 · VCV2526633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6144 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6144	likely pathogenic
REVEL	0.056	moderately benign-leaning
SaProt	LLR -9.25	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 7.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 136 bp · p 8.4e-05 · regional, not allelic
Overall
CADD	28.0	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: SP9
Protein: p.Ser448Phe
Coding: c.1343C>T
MANE Select: NM_001145250
dbSNP: rs981960411
Type: single nucleotide variant
Location: chr2:174337428 (GRCh38)
Gene constraint: LOEUF 0.731 · pLI 0.58 (gnomAD)
Structure: AlphaFold pLDDT 49.04

Full SP9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SP9 p.Ser112Ala Uncertain significance ★★ ⚠ same type
SP9 p.Ala462= Likely benign ★★ same type
SP9 p.Glu378Gly Pathogenic ★ same type
SP9 p.Ser82Ter Pathogenic ★ same type
SP9 p.Ala176Val Uncertain significance ★ ⚠ same type
SP9 p.Ala241Ser Uncertain significance ★ ⚠ same type
SP9 p.Ala242Thr Uncertain significance ★ ⚠ same type
SP9 p.Ala393Ser 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/sp9-p-ser448phe (accessed [today's date]).

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