Is SDHD p.His102= (c.306T>C) pathogenic?

SDHD p.His102= (c.306T>C) is classified Likely benign in SDHD (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-15). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SDHD p.His102= (c.306T>C)?

SDHD p.His102= (c.306T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SDHD p.His102= (c.306T>C) in the general population?

SDHD p.His102= (c.306T>C) is absent from gnomAD v4.1 (gnomAD).

SDHD p.His102=

c.306T>C · rs2498905606 · VCV1799489

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	<0.2	all four deltas below 0.2 · T>A here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.3	GERP -4.3
Overall
CADD	0.935	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: SDHD
Protein: p.His102=
Coding: c.306T>C
MANE Select: NM_003002
dbSNP: rs2498905606
Type: single nucleotide variant
Location: chr11:112089003 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB
Residue 102: a UniProt-annotated variant site (in ppgl1); an α-helix; a binding site

Full SDHD 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

SDHD p.His102Arg Pathogenic/Likely pathogenic ★★ same residue
SDHD p.His102Asn Pathogenic/Likely pathogenic ★★ same residue
SDHD p.His102Leu Pathogenic ★★ same residue
SDHD p.His102Pro Pathogenic/Likely pathogenic ★★ same residue
SDHD p.His102Tyr Pathogenic/Likely pathogenic ★★ ⚠ same residue
SDHD p.His102fs Pathogenic/Likely pathogenic ★★ same residue
SDHD c.170-1G>T Pathogenic ★★ same condition
SDHD c.170-2A>G Pathogenic/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/sdhd-p-his102 (accessed [today's date]).

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