Is SDHC p.Pro93Ser (c.277C>T) pathogenic?

SDHC p.Pro93Ser (c.277C>T) is classified Uncertain significance in SDHC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-24). AlphaMissense: likely benign (0.2637); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SDHC p.Pro93Ser (c.277C>T)?

SDHC p.Pro93Ser (c.277C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SDHC p.Pro93Ser (c.277C>T) in the general population?

SDHC p.Pro93Ser (c.277C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SDHC p.Pro93Ser (c.277C>T)?

AlphaMissense predicts likely benign (score 0.2637) — an in-silico prediction, not a clinical call.

SDHC p.Pro93Ser

c.277C>T · VCV3438780

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2637 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2637	likely benign
REVEL	0.55	indeterminate
SaProt	LLR -12.65	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 22 kb · p 1.5e-06 · regional, not allelic
Overall
CADD	24.4	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: SDHC
Protein: p.Pro93Ser
Coding: c.277C>T
MANE Select: NM_003001
Type: single nucleotide variant
Location: chr1:161356712 (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.Pro93Leu Uncertain significance ★★ ⚠ same residue
SDHC p.Pro93= Benign/Likely benign ★★ 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
SDHC c.405+1G>A Pathogenic ★★ same condition
SDHC c.405+1G>C 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-pro93ser (accessed [today's date]).

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