Is SDHB p.Val124Phe (c.370G>T) pathogenic?

SDHB p.Val124Phe (c.370G>T) is classified Uncertain significance in SDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: likely benign (0.2801); Absent from gnomAD v4.1.

How common is SDHB p.Val124Phe (c.370G>T) in the general population?

SDHB p.Val124Phe (c.370G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SDHB p.Val124Phe (c.370G>T)?

AlphaMissense predicts likely benign (score 0.2801) — an in-silico prediction, not a clinical call.

SDHB p.Val124Phe

c.370G>T · VCV3893533

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2801 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2801	likely benign
REVEL	0.554	indeterminate
SaProt	LLR -11.42	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.34	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 35 kb · p 0.67 · regional, not allelic
Overall
CADD	27.6	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

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: SDHB
Protein: p.Val124Phe
Coding: c.370G>T
MANE Select: NM_003000
Type: single nucleotide variant
Location: chr1:17028653 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 124: the 2fe-2s ferredoxin-type domain; a β-strand

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

Similar variants

SDHB p.Val124Ala Uncertain significance ★ ⚠ same residue
SDHB p.Val124Ile Uncertain significance ★ ⚠ same residue
SDHB p.Val124fs Pathogenic same residue
SDHB c.200+1G>A Pathogenic ★★ same type
SDHB c.200+1G>C Pathogenic/Likely pathogenic ★★ same type
SDHB c.200+5G>T Likely pathogenic ★★ same type
SDHB c.201-1G>C Pathogenic/Likely pathogenic ★★ same type
SDHB c.201-2A>C Pathogenic ★★ same type

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/sdhb-p-val124phe (accessed [today's date]).

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