Is SDHA p.Phe62Val (c.184T>G) pathogenic?

SDHA p.Phe62Val (c.184T>G) is classified Uncertain significance in SDHA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-21). AlphaMissense: likely pathogenic (0.9301); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SDHA p.Phe62Val (c.184T>G)?

SDHA p.Phe62Val (c.184T>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SDHA p.Phe62Val (c.184T>G) in the general population?

SDHA p.Phe62Val (c.184T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SDHA p.Phe62Val (c.184T>G)?

AlphaMissense predicts likely pathogenic (score 0.9301) — an in-silico prediction, not a clinical call.

SDHA p.Phe62Val

c.184T>G · VCV4161181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9301 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9301	likely pathogenic
REVEL	0.67	pathogenic-leaning
SaProt	LLR -10.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 38 kb · p 1.1e-12 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: SDHA
Protein: p.Phe62Val
Coding: c.184T>G
MANE Select: NM_004168
Type: single nucleotide variant
Location: chr5:224393 (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.Phe62= Likely benign ★ 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-phe62val (accessed [today's date]).

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