Is SDHAF2 p.Phe34Val (c.100T>G) pathogenic?

SDHAF2 p.Phe34Val (c.100T>G) is classified Uncertain significance in SDHAF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0906); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SDHAF2 p.Phe34Val (c.100T>G)?

SDHAF2 p.Phe34Val (c.100T>G) is associated with hereditary neoplastic syndrome, hereditary pheochromocytoma-paraganglioma (ClinVar).

How common is SDHAF2 p.Phe34Val (c.100T>G) in the general population?

SDHAF2 p.Phe34Val (c.100T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SDHAF2 p.Phe34Val (c.100T>G)?

AlphaMissense predicts likely benign (score 0.0906) — an in-silico prediction, not a clinical call.

SDHAF2 p.Phe34Val

c.100T>G · rs756917732 · VCV822005

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0906 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0906	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -7.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 16 kb · p 0.71 · regional, not allelic
Overall
CADD	18.72	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: SDHAF2
Protein: p.Phe34Val
Coding: c.100T>G
MANE Select: NM_017841
dbSNP: rs756917732
Type: single nucleotide variant
Location: chr11:61437688 (GRCh38)
Gene constraint: LOEUF 1.608 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.06 · 2 PDB

Full SDHAF2 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: hereditary pheochromocytoma-paraganglioma

Similar variants

SDHAF2 p.Phe34Leu Uncertain significance ★★ ⚠ same residue
SDHAF2 p.Phe34Ser Uncertain significance ★ ⚠ same residue
SDHAF2 c.260+1G>A Likely pathogenic ★★ same condition
SDHAF2 c.261-2A>G Likely pathogenic ★★ same condition
SDHAF2 c.261-2A>T Likely pathogenic ★★ same condition
SDHAF2 c.37-1G>C Pathogenic/Likely pathogenic ★★ same condition
SDHAF2 c.37-2A>G Pathogenic/Likely pathogenic ★★ same condition
SDHAF2 c.370+1G>T 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/sdhaf2-p-phe34val (accessed [today's date]).

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