Is CISD2 p.Ala7= (c.21C>T) pathogenic?

CISD2 p.Ala7= (c.21C>T) is classified Likely benign in CISD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-10). Very rare (popmax 0.00534%, afr).

How common is CISD2 p.Ala7= (c.21C>T) in the general population?

CISD2 p.Ala7= (c.21C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

CISD2 p.Ala7=

c.21C>T · rs1055484125 · VCV2985658

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

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 0.8	GERP -1.2, phastCons 1
Overall
CADD	13.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,914 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,612,216 alleles · very rare

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: CISD2
Protein: p.Ala7=
Coding: c.21C>T
MANE Select: NM_001008388
dbSNP: rs1055484125
Type: single nucleotide variant
Location: chr4:102869105 (GRCh38)
Gene constraint: LOEUF 0.437 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 90.19 · 4 PDB

Full CISD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CISD2 p.Ala7Thr Uncertain significance ★ ⚠ same residue
CISD2 c.103+6C>A Uncertain significance ★★ same type
CISD2 p.Arg57Cys Uncertain significance ★★ ⚠ same type
CISD2 p.Arg57His Uncertain significance ★★ ⚠ same type
CISD2 p.Asn87Ser Uncertain significance ★★ ⚠ same type
CISD2 p.Glu4Gln Uncertain significance ★★ ⚠ same type
CISD2 p.Pro61Leu Uncertain significance ★★ ⚠ same type
CISD2 p.Pro80Leu Uncertain significance ★★ ⚠ 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/cisd2-p-ala7 (accessed [today's date]).

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