Is SDHC p.Phe118= (c.354T>C) pathogenic?

SDHC p.Phe118= (c.354T>C) is classified Benign/Likely benign in SDHC (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.47%, afr); Associated with pheochromocytoma/paraganglioma syndrome 3.

What condition is associated with SDHC p.Phe118= (c.354T>C)?

SDHC p.Phe118= (c.354T>C) is associated with pheochromocytoma/paraganglioma syndrome 3, gastrointestinal stromal tumor, hereditary neoplastic syndrome (ClinVar).

How common is SDHC p.Phe118= (c.354T>C) in the general population?

SDHC p.Phe118= (c.354T>C) is low-frequency (popmax 1.47%, afr) (gnomAD).

SDHC p.Phe118=

c.354T>C · rs61733156 · VCV165182

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.47%, afr)

Conditions

pheochromocytoma/paraganglioma syndrome 3

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 -0.044	GERP 0.46, phastCons 0.9
Overall
CADD	8.164	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.47% African / African-American · 1,100/75,042 alleles

Filtering AF 1.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.36%

Overall 0.0737% 1,190/1,614,176 alleles · low-frequency exomes 565/1,461,884 · genomes 625/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.47%	68
Middle Eastern	0.099%	1,010
Remaining individualsnot grpmax-eligible	0.08%	1,250
Admixed American	0.04%	2,501
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
European (non-Finnish)	0.000763%	131,114

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.Phe118=
Coding: c.354T>C
MANE Select: NM_003001
dbSNP: rs61733156
Type: single nucleotide variant
Location: chr1:161356789 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 91.05 · 2 PDB
Residue 118: an α-helix

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

Disease context

pheochromocytoma/paraganglioma syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastrointestinal stromal tumor hereditary neoplastic syndrome Cowden disease hereditary pheochromocytoma-paraganglioma

Similar variants

SDHC p.Phe118Leu 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
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

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-phe118 (accessed [today's date]).

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