Is SDHC p.Pro54Ala (c.160C>G) pathogenic?

SDHC p.Pro54Ala (c.160C>G) is classified Uncertain significance in SDHC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: likely pathogenic (0.9068); Absent from gnomAD v4.1; Associated with gastrointestinal stromal tumor.

What condition is associated with SDHC p.Pro54Ala (c.160C>G)?

SDHC p.Pro54Ala (c.160C>G) is associated with gastrointestinal stromal tumor, pheochromocytoma/paraganglioma syndrome 3 (ClinVar).

How common is SDHC p.Pro54Ala (c.160C>G) in the general population?

SDHC p.Pro54Ala (c.160C>G) is absent from gnomAD v4.1 (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.Pro54Ala (c.160C>G)?

AlphaMissense predicts likely pathogenic (score 0.9068) — an in-silico prediction, not a clinical call.

SDHC p.Pro54Ala

c.160C>G · VCV3757251

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9068 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
AlphaMissense	0.9068	likely pathogenic
REVEL	0.972	strongly pathogenic-leaning
SaProt	LLR -13.48	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 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 26 kb · p 0.78 · regional, not allelic
Overall
CADD	23.5	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

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: SDHC
Protein: p.Pro54Ala
Coding: c.160C>G
MANE Select: NM_003001
Type: single nucleotide variant
Location: chr1:161328478 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 91.05 · 2 PDB

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.Pro54Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHC p.Pro54Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHC p.Pro54Leu Uncertain significance ★ ⚠ same residue
SDHC p.Pro54= Likely benign ★ 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
SDHC c.20+1G>T 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-pro54ala (accessed [today's date]).

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