Is SDHC p.Pro54= (c.162C>G) pathogenic?

SDHC p.Pro54= (c.162C>G) is classified Likely benign in SDHC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-11). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SDHC p.Pro54= (c.162C>G)?

SDHC p.Pro54= (c.162C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SDHC p.Pro54= (c.162C>G) in the general population?

SDHC p.Pro54= (c.162C>G) is absent from gnomAD v4.1 (gnomAD).

SDHC p.Pro54=

c.162C>G · VCV3438777

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.2	GERP -3.1
Overall
CADD	0.439	PHRED · no single calibrated threshold — expert panels disagree

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.Pro54=
Coding: c.162C>G
MANE Select: NM_003001
Type: single nucleotide variant
Location: chr1:161328480 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SDHC p.Pro54Leu Uncertain significance ★ ⚠ same residue
SDHC p.Pro54Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHC p.Pro54Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHC p.Pro54Ala Uncertain significance ★ ⚠ same residue
SDHC c.179+1G>C Likely pathogenic ★★ same condition
SDHC c.180-2A>G Likely pathogenic ★★ same condition
SDHC c.21-2A>G Pathogenic/Likely pathogenic ★★ same condition
SDHC c.241+1G>A 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-pro54 (accessed [today's date]).

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