SLC4A4 p.Phe773=
c.2319T>C · rs138535007 · VCV3033498
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.135%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.45 | GERP -3.5, phastCons 0.18 |
| Overall | ||
| CADD | 3.319 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.135%
African / African-American · 101/74,904 alleles
Filtering AF
0.113%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.106%
Overall
0.00713%
115/1,613,588 alleles · rare
exomes 53/1,461,460 · genomes 62/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.135% | 742 |
| Middle Eastern | 0.0658% | 1,520 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,921 |
| Admixed American | 0.00501% | 19,976 |
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
- SLC4A4
- Protein
- p.Phe773=
- Coding
- c.2319T>C
- MANE Select
- NM_001098484
- dbSNP
- rs138535007
- Type
- single nucleotide variant
- Location
- chr4:71534265 (GRCh38)
- Gene constraint
- LOEUF 0.329 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.77 · 1 PDB
- Residue 773
- the 'interaction with ca4' region
Similar variants
- SLC4A4 c.1208+4A>C Uncertain significance ★★ same type
- SLC4A4 c.1322+5C>T Uncertain significance ★★ same type
- SLC4A4 c.*26G>T Uncertain significance ★★ same type
- SLC4A4 p.Ala454Thr Uncertain significance ★★ ⚠ same type
- SLC4A4 p.Ala454Val Uncertain significance ★★ ⚠ same type
- SLC4A4 p.Ala667Thr Uncertain significance ★★ ⚠ same type
- SLC4A4 p.Ala744Val Uncertain significance ★★ ⚠ same type
- SLC4A4 p.Ala817Thr 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/slc4a4-p-phe773 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown