Is SDHD p.Asp92Val (c.275A>T) pathogenic?

SDHD p.Asp92Val (c.275A>T) is classified Likely pathogenic in SDHD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-23). AlphaMissense: likely pathogenic (0.9607); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SDHD p.Asp92Val (c.275A>T)?

SDHD p.Asp92Val (c.275A>T) is associated with hereditary neoplastic syndrome, pheochromocytoma, Carney-Stratakis syndrome (ClinVar).

How common is SDHD p.Asp92Val (c.275A>T) in the general population?

SDHD p.Asp92Val (c.275A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SDHD p.Asp92Val (c.275A>T)?

AlphaMissense predicts likely pathogenic (score 0.9607) — an in-silico prediction, not a clinical call.

SDHD p.Asp92Val

c.275A>T · rs786205436 · VCV420665

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9607 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9607	likely pathogenic ✓ concordant with ClinVar · top 3% in SDHD
REVEL	0.992	strongly pathogenic-leaning
SaProt	LLR -16.68	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.23	donor loss · deltas
Pangolin	Δ0.22	loss · gain 0.00 · agrees with SpliceAI · independent
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	29.0	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.Asp92Val
Coding: c.275A>T
MANE Select: NM_003002
dbSNP: rs786205436
Type: single nucleotide variant
Location: chr11:112088972 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB
Residue 92: a UniProt-annotated variant site (in mc2dn3; results in highly reduced protein expression; results in impaired cellular respiration); a UniProt-annotated variant site (in ppgl1); an α-helix

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

Also linked: pheochromocytoma Carney-Stratakis syndrome Cowden syndrome 3

Similar variants

SDHD p.Asp92Tyr Pathogenic/Likely pathogenic ★★ same residue
SDHD p.Asp92Glu Uncertain significance ★★ ⚠ same residue
SDHD p.Asp92Asn Uncertain significance ★ ⚠ same residue
SDHD p.Asp92= Likely benign ★ same residue
SDHD p.Asp92fs Pathogenic ★ same residue
SDHD p.Asp92Gly 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-asp92val (accessed [today's date]).

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