Is SDHAF2 p.Arg18= (c.54G>A) pathogenic?

SDHAF2 p.Arg18= (c.54G>A) is classified Likely benign in SDHAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with SDHAF2 p.Arg18= (c.54G>A)?

SDHAF2 p.Arg18= (c.54G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SDHAF2 p.Arg18= (c.54G>A) in the general population?

SDHAF2 p.Arg18= (c.54G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

SDHAF2 p.Arg18=

c.54G>A · VCV3951371

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.74	GERP -5, phastCons 0.12
Overall
CADD	8.499	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,076 alleles

Overall 0.000124% 2/1,613,898 alleles · very rare exomes 1/1,461,748 · genomes 1/152,150 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,076
European (non-Finnish)	8.48e-05%	1,179,912

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: SDHAF2
Protein: p.Arg18=
Coding: c.54G>A
MANE Select: NM_017841
Type: single nucleotide variant
Location: chr11:61437642 (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

Similar variants

SDHAF2 p.Arg18Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHAF2 p.Arg18Lys 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-arg18 (accessed [today's date]).

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