Is SDHD p.Val111= (c.333T>C) pathogenic?

SDHD p.Val111= (c.333T>C) is classified Uncertain significance in SDHD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). Absent from gnomAD v4.1.

How common is SDHD p.Val111= (c.333T>C) in the general population?

SDHD p.Val111= (c.333T>C) is absent from gnomAD v4.1 (gnomAD).

SDHD p.Val111=

c.333T>C · VCV3905990

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.377	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -4.3, phastCons 0.002
Overall
CADD	7.712	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.Val111=
Coding: c.333T>C
MANE Select: NM_003002
Type: single nucleotide variant
Location: chr11:112094823 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB
Residue 111: an α-helix

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

Similar variants

SDHD p.Val111Ala Uncertain significance ★★ ⚠ same residue
SDHD p.Val111Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHD p.Val111Leu Uncertain significance ★ ⚠ same residue
SDHD p.Val111Phe Uncertain significance ★ ⚠ same residue
SDHD p.Val111delinsPhePheArgGlyLeuGlnTer Pathogenic ★ same residue
SDHD p.Val111del Uncertain significance ★ same residue
SDHD c.170-1G>T Pathogenic ★★ same type
SDHD c.170-2A>G Pathogenic/Likely pathogenic ★★ same type

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-val111 (accessed [today's date]).

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