Is SDHA p.Phe62= (c.186T>C) pathogenic?

SDHA p.Phe62= (c.186T>C) is classified Likely benign in SDHA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-07). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SDHA p.Phe62= (c.186T>C)?

SDHA p.Phe62= (c.186T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SDHA p.Phe62= (c.186T>C) in the general population?

SDHA p.Phe62= (c.186T>C) is absent from gnomAD v4.1 (gnomAD).

SDHA p.Phe62=

c.186T>C · rs2477285660 · VCV1781672

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP 1.8, phastCons 1
Overall
CADD	10.22	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: SDHA
Protein: p.Phe62=
Coding: c.186T>C
MANE Select: NM_004168
dbSNP: rs2477285660
Type: single nucleotide variant
Location: chr5:224395 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 5 PDB
Residue 62: a β-strand

Full SDHA 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

SDHA p.Phe62Val Uncertain significance ★ ⚠ same residue
SDHA p.Phe62fs Pathogenic ★ same residue
SDHA p.Phe62Leu Uncertain significance ★ ⚠ same residue
SDHA c.1064+1G>T Likely pathogenic ★★ same condition
SDHA c.1064+2T>A Likely pathogenic ★★ same condition
SDHA c.1261-1G>A Likely pathogenic ★★ same condition
SDHA c.1261-2A>G Likely pathogenic ★★ same condition
SDHA c.151-1G>C 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/sdha-p-phe62 (accessed [today's date]).

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