Is SDHC p.Phe85= (c.255T>C) pathogenic?

SDHC p.Phe85= (c.255T>C) is classified Likely benign in SDHC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-02). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SDHC p.Phe85= (c.255T>C)?

SDHC p.Phe85= (c.255T>C) is associated with hereditary neoplastic syndrome, pheochromocytoma/paraganglioma syndrome 3, gastrointestinal stromal tumor (ClinVar).

How common is SDHC p.Phe85= (c.255T>C) in the general population?

SDHC p.Phe85= (c.255T>C) is absent from gnomAD v4.1 (gnomAD).

SDHC p.Phe85=

c.255T>C · rs2102370353 · VCV1554672

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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	<0.2	all four deltas below 0.2 · T>A here scores Δ0.47 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.46	GERP 1.5, phastCons 1
Overall
CADD	9.555	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.Phe85=
Coding: c.255T>C
MANE Select: NM_003001
dbSNP: rs2102370353
Type: single nucleotide variant
Location: chr1:161356690 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 91.05 · 2 PDB
Residue 85: an α-helix

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

Also linked: pheochromocytoma/paraganglioma syndrome 3 gastrointestinal stromal tumor

Similar variants

SDHC p.Phe85Cys Uncertain significance ★★ ⚠ same residue
SDHC p.Phe85Ser Uncertain significance ★ ⚠ same residue
SDHC p.Phe85fs Pathogenic ★ same residue
SDHC p.Phe85Lys 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
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-phe85 (accessed [today's date]).

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