Is SDHD p.His102Pro (c.305A>C) pathogenic?

SDHD p.His102Pro (c.305A>C) is classified Pathogenic/Likely pathogenic in SDHD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-15). AlphaMissense: likely pathogenic (0.7574); Absent from gnomAD v4.1; Associated with pheochromocytoma.

What condition is associated with SDHD p.His102Pro (c.305A>C)?

SDHD p.His102Pro (c.305A>C) is associated with pheochromocytoma, Carney-Stratakis syndrome, Cowden syndrome 3 (ClinVar).

How common is SDHD p.His102Pro (c.305A>C) in the general population?

SDHD p.His102Pro (c.305A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SDHD p.His102Pro (c.305A>C)?

AlphaMissense predicts likely pathogenic (score 0.7574) — an in-silico prediction, not a clinical call.

SDHD p.His102Pro

c.305A>C · rs104894302 · VCV950869

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7574 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pheochromocytoma

Computational evidence

Protein change
AlphaMissense	0.7574	likely pathogenic ✓ concordant with ClinVar
REVEL	0.929	moderately pathogenic-leaning
SaProt	LLR -14.47	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 8,059 bp · p 0.019 · regional, not allelic
Overall
CADD	27.2	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: SDHD
Protein: p.His102Pro
Coding: c.305A>C
MANE Select: NM_003002
dbSNP: rs104894302
Type: single nucleotide variant
Location: chr11:112089002 (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

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

Also linked: Carney-Stratakis syndrome Cowden syndrome 3 hereditary neoplastic syndrome

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.His102Tyr Pathogenic/Likely pathogenic ★★ ⚠ same residue
SDHD p.His102= Likely benign ★ 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-his102pro (accessed [today's date]).

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