Is SDHC p.Ser151Phe (c.452C>T) pathogenic?

SDHC p.Ser151Phe (c.452C>T) is classified Uncertain significance in SDHC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-30). AlphaMissense: likely pathogenic (0.903); Very rare (popmax 8.48e-05%, nfe); Associated with gastrointestinal stromal tumor.

What condition is associated with SDHC p.Ser151Phe (c.452C>T)?

SDHC p.Ser151Phe (c.452C>T) is associated with gastrointestinal stromal tumor, pheochromocytoma/paraganglioma syndrome 3 (ClinVar).

How common is SDHC p.Ser151Phe (c.452C>T) in the general population?

SDHC p.Ser151Phe (c.452C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Gastrointestinal stromal tumor inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SDHC p.Ser151Phe (c.452C>T)?

AlphaMissense predicts likely pathogenic (score 0.903) — an in-silico prediction, not a clinical call.

SDHC p.Ser151Phe

c.452C>T · rs1571899020 · VCV2942066

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
AlphaMissense	0.903	likely pathogenic
REVEL	0.869	moderately pathogenic-leaning
SaProt	LLR -14.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 22 kb · p 1.5e-06 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.48e-05% European (non-Finnish) · 1/1,179,732 alleles

Overall 6.2e-05% 1/1,612,658 alleles · very rare exomes 1/1,461,596 · genomes 0/151,062 · 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: SDHC
Protein: p.Ser151Phe
Coding: c.452C>T
MANE Select: NM_003001
dbSNP: rs1571899020
Type: single nucleotide variant
Location: chr1:161362375 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 91.05 · 2 PDB
Residue 151: an α-helix

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

Disease context

gastrointestinal stromal tumor — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma/paraganglioma syndrome 3

For Gastrointestinal stromal tumor (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SDHC p.Ser151Cys Uncertain significance ★★ ⚠ same residue
SDHC p.Ser151Pro Uncertain significance ★★ ⚠ same residue
SDHC p.Ser151Tyr Uncertain significance ★★ ⚠ same residue
SDHC p.Ser151= Likely benign ★ same residue
SDHC p.Ser151Thr Uncertain significance ★ ⚠ same residue
SDHC c.179+1G>C Likely pathogenic ★★ same condition
SDHC c.179+1G>T Likely pathogenic ★★ same condition
SDHC c.180-2A>G Likely pathogenic ★★ 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/sdhc-p-ser151phe (accessed [today's date]).

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