Is SDHD p.Pro24Leu (c.71C>T) pathogenic?

SDHD p.Pro24Leu (c.71C>T) is classified Uncertain significance in SDHD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-28). AlphaMissense: likely benign (0.1064); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SDHD p.Pro24Leu (c.71C>T)?

SDHD p.Pro24Leu (c.71C>T) is associated with hereditary neoplastic syndrome, pheochromocytoma, Carney-Stratakis syndrome (ClinVar).

How common is SDHD p.Pro24Leu (c.71C>T) in the general population?

SDHD p.Pro24Leu (c.71C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SDHD p.Pro24Leu (c.71C>T)?

AlphaMissense predicts likely benign (score 0.1064) — an in-silico prediction, not a clinical call.

SDHD p.Pro24Leu

c.71C>T · rs1865651909 · VCV1397142

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1064 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1064	likely benign
REVEL	0.558	indeterminate
SaProt	LLR -8.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.25	acceptor loss, 18 bp away · masked 0 · deltas
Pangolin	Δ0.27	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.57	GERP -2
Regional constraint	o/e 0.83	unconstrained · MANE · 8,059 bp · p 0.019 · regional, not allelic
Overall
CADD	14.33	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Pro24Leu
Coding: c.71C>T
MANE Select: NM_003002
dbSNP: rs1865651909
Type: single nucleotide variant
Location: chr11:112087875 (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

Also linked: pheochromocytoma Carney-Stratakis syndrome Cowden syndrome 3

Similar variants

SDHD p.Pro24= Likely benign ★★ same residue
SDHD p.Pro24Ala Uncertain significance ★ ⚠ same residue
SDHD p.Pro24Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHD p.Pro24fs Pathogenic ★ 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

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-pro24leu (accessed [today's date]).

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