Is SDHC p.His8= (c.24C>T) pathogenic?

SDHC p.His8= (c.24C>T) is classified Benign/Likely benign in SDHC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-13). Very rare (popmax 0.00333%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with SDHC p.His8= (c.24C>T)?

SDHC p.His8= (c.24C>T) is associated with hereditary neoplastic syndrome, pheochromocytoma/paraganglioma syndrome 3, gastrointestinal stromal tumor (ClinVar).

How common is SDHC p.His8= (c.24C>T) in the general population?

SDHC p.His8= (c.24C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

SDHC p.His8=

c.24C>T · rs761381438 · VCV465968

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 · C>G here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.025	GERP -2.1, phastCons 0.82
Overall
CADD	4.664	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,994 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00105% 17/1,612,766 alleles · very rare exomes 16/1,460,620 · genomes 1/152,146 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,997
South Asian	0.00329%	30,355
Remaining individualsnot grpmax-eligible	0.0032%	31,217
East Asian	0.00223%	44,882
African / African-American	0.00134%	74,862
European (non-Finnish)	0.000679%	147,369

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.His8=
Coding: c.24C>T
MANE Select: NM_003001
dbSNP: rs761381438
Type: single nucleotide variant
Location: chr1:161323617 (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

Also linked: pheochromocytoma/paraganglioma syndrome 3 gastrointestinal stromal tumor hereditary pheochromocytoma-paraganglioma

Similar variants

SDHC p.His8Arg Uncertain significance ★★ ⚠ same residue
SDHC p.His8Asn Uncertain significance ★★ ⚠ same residue
SDHC p.His8Gln Uncertain significance ★★ ⚠ same residue
SDHC p.His8Tyr Uncertain significance ★★ ⚠ same residue
SDHC p.His8Pro Uncertain significance ★ ⚠ same residue
SDHC p.His8fs Pathogenic ★★ same residue
SDHC c.179+1G>C Likely pathogenic ★★ same condition
SDHC c.179+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-his8 (accessed [today's date]).

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