Is SDHD p.Ala124= (c.372C>G) pathogenic?

SDHD p.Ala124= (c.372C>G) is classified Benign/Likely benign in SDHD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-18). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SDHD p.Ala124= (c.372C>G)?

SDHD p.Ala124= (c.372C>G) is associated with hereditary neoplastic syndrome, pheochromocytoma/paraganglioma syndrome 1, pheochromocytoma (ClinVar).

How common is SDHD p.Ala124= (c.372C>G) in the general population?

SDHD p.Ala124= (c.372C>G) is absent from gnomAD v4.1 (gnomAD).

SDHD p.Ala124=

c.372C>G · rs2135277535 · VCV1104611

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.324	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.39, phastCons 1
Overall
CADD	12.94	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.Ala124=
Coding: c.372C>G
MANE Select: NM_003002
dbSNP: rs2135277535
Type: single nucleotide variant
Location: chr11:112094862 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB
Residue 124: 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/paraganglioma syndrome 1 pheochromocytoma Carney-Stratakis syndrome Cowden syndrome 3

Similar variants

SDHD p.Ala124Ser Uncertain significance ★★ ⚠ same residue
SDHD p.Ala124Thr Uncertain significance ★★ ⚠ same residue
SDHD p.Ala124Val 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-ala124 (accessed [today's date]).

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