Is SDHD p.Ser32= (c.96A>C) pathogenic?

SDHD p.Ser32= (c.96A>C) is classified Likely benign in SDHD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-11). Very rare (popmax 0.000424%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with SDHD p.Ser32= (c.96A>C)?

SDHD p.Ser32= (c.96A>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SDHD p.Ser32= (c.96A>C) in the general population?

SDHD p.Ser32= (c.96A>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

SDHD p.Ser32=

c.96A>C · rs2498899823 · VCV1767864

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.84	GERP -1.6, phastCons 0.98
Overall
CADD	8.989	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,036 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,042 alleles · very rare exomes 5/1,460,796 · genomes 0/152,246 · joint denominator

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: SDHD
Protein: p.Ser32=
Coding: c.96A>C
MANE Select: NM_003002
dbSNP: rs2498899823
Type: single nucleotide variant
Location: chr11:112087900 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB

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.Ser32Ter Pathogenic ★ same residue
SDHD p.Ser32Ala Uncertain significance ★ ⚠ same residue
SDHD p.Ser32Leu Uncertain significance ★ ⚠ same residue
SDHD c.170-1G>T Pathogenic ★★ same condition
SDHD c.170-2A>G Pathogenic/Likely pathogenic ★★ same condition
SDHD c.314+1G>A Pathogenic ★★ same condition
SDHD c.314+1G>T Pathogenic ★★ same condition
SDHD c.315-1G>A 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-ser32 (accessed [today's date]).

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