Is SLC4A4 p.Pro1007= (c.3021A>T) pathogenic?

SLC4A4 p.Pro1007= (c.3021A>T) is classified Likely benign in SLC4A4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). Ultra-rare (popmax 0.0923%, afr).

How common is SLC4A4 p.Pro1007= (c.3021A>T) in the general population?

SLC4A4 p.Pro1007= (c.3021A>T) is ultra-rare (popmax 0.0923%, afr) (gnomAD).

SLC4A4 p.Pro1007=

c.3021A>T · rs144619583 · VCV2143464

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0923%, 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 7.8	GERP 0.48, phastCons 1
Overall
CADD	12.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0923% African / African-American · 69/74,752 alleles

Filtering AF 0.0747% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0684%

Overall 0.00484% 78/1,611,284 alleles · ultra-rare exomes 33/1,459,454 · genomes 45/151,830 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0923%	1,083
Middle Eastern	0.0165%	6,072
Admixed American	0.01%	9,965
Remaining individualsnot grpmax-eligible	0.00321%	31,163

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.Pro1007=
Coding: c.3021A>T
MANE Select: NM_001098484
dbSNP: rs144619583
Type: single nucleotide variant
Location: chr4:71560176 (GRCh38)
Gene constraint: LOEUF 0.329 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 1 PDB

Full SLC4A4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-pro1007 (accessed [today's date]).

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