Is SDHC p.Val82Phe (c.244G>T) pathogenic?

SDHC p.Val82Phe (c.244G>T) is classified Uncertain significance in SDHC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-09). AlphaMissense: likely benign (0.2452); Very rare (popmax 0.00167%, amr); Associated with pheochromocytoma/paraganglioma syndrome 3.

What condition is associated with SDHC p.Val82Phe (c.244G>T)?

SDHC p.Val82Phe (c.244G>T) is associated with pheochromocytoma/paraganglioma syndrome 3, gastrointestinal stromal tumor, hereditary neoplastic syndrome (ClinVar).

How common is SDHC p.Val82Phe (c.244G>T) in the general population?

SDHC p.Val82Phe (c.244G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about SDHC p.Val82Phe (c.244G>T)?

AlphaMissense predicts likely benign (score 0.2452) — an in-silico prediction, not a clinical call.

SDHC p.Val82Phe

c.244G>T · rs570325845 · VCV407061

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2452 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pheochromocytoma/paraganglioma syndrome 3

Computational evidence

Protein change
AlphaMissense	0.2452	likely benign
REVEL	0.717	pathogenic-leaning
SaProt	LLR -10.18	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -1.2, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 22 kb · p 1.5e-06 · regional, not allelic
Overall
CADD	21.0	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

Grpmax group 0.00167% Admixed American · 1/60,006 alleles

Overall 6.2e-05% 1/1,613,868 alleles · very rare exomes 0/1,461,588 · genomes 1/152,280 · 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: SDHC
Protein: p.Val82Phe
Coding: c.244G>T
MANE Select: NM_003001
dbSNP: rs570325845
Type: single nucleotide variant
Location: chr1:161356679 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 91.05 · 2 PDB
Residue 82: an α-helix

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

Disease context

pheochromocytoma/paraganglioma syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

SDHC p.Val82Ile Uncertain significance ★★ ⚠ same residue
SDHC p.Val82= Likely benign ★★ same residue
SDHC c.179+1G>C Likely pathogenic ★★ same condition
SDHC c.179+1G>T Likely pathogenic ★★ same condition
SDHC c.180-2A>G Likely pathogenic ★★ same condition
SDHC c.20+1G>T Likely pathogenic ★★ same condition
SDHC c.21-2A>G Pathogenic/Likely pathogenic ★★ same condition
SDHC c.241+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/sdhc-p-val82phe (accessed [today's date]).

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