Is SPEG p.Ser162Phe (c.485C>T) pathogenic?

SPEG p.Ser162Phe (c.485C>T) is classified Uncertain significance in SPEG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-25). AlphaMissense: ambiguous (0.4127); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SPEG p.Ser162Phe (c.485C>T)?

SPEG p.Ser162Phe (c.485C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SPEG p.Ser162Phe (c.485C>T) in the general population?

SPEG p.Ser162Phe (c.485C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SPEG p.Ser162Phe (c.485C>T)?

AlphaMissense predicts ambiguous (score 0.4127) — an in-silico prediction, not a clinical call.

SPEG p.Ser162Phe

c.485C>T · VCV3448369

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4127 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4127	ambiguous
REVEL	0.257	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 27 kb · p 0.32 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: SPEG
Protein: p.Ser162Phe
Coding: c.485C>T
MANE Select: NM_005876
Type: single nucleotide variant
Location: chr2:219444831 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI <0.01 (gnomAD)
Residue 162: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPEG p.Ala1249Thr Uncertain significance ★★ ⚠ same condition
SPEG p.Ala1334Val Uncertain significance ★★ ⚠ same condition
SPEG p.Ala1628Val Uncertain significance ★★ same condition
SPEG p.Ala1686Thr Uncertain significance ★★ ⚠ same condition
SPEG p.Ala199Val Uncertain significance ★★ ⚠ same condition
SPEG p.Ala220Ser Uncertain significance ★★ ⚠ same condition
SPEG p.Ala241Thr Uncertain significance ★★ ⚠ same condition
SPEG p.Ala291Gly 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/speg-p-ser162phe (accessed [today's date]).

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