Is SLC4A4 p.Arg441= (c.1321C>A) pathogenic?

SLC4A4 p.Arg441= (c.1321C>A) is classified Uncertain significance in SLC4A4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-16). No allele count reported in gnomAD v4.1 (AN 1,578,406); Associated with autosomal recessive proximal renal tubular acidosis.

What condition is associated with SLC4A4 p.Arg441= (c.1321C>A)?

SLC4A4 p.Arg441= (c.1321C>A) is associated with autosomal recessive proximal renal tubular acidosis (ClinVar).

How common is SLC4A4 p.Arg441= (c.1321C>A) in the general population?

SLC4A4 p.Arg441= (c.1321C>A) is no allele count reported in gnomAD v4.1 (AN 1,578,406) (gnomAD).

How is Proximal renal tubular acidosis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SLC4A4 p.Arg441=

c.1321C>A · VCV3590791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,578,406)

Conditions

autosomal recessive proximal renal tubular acidosis

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 1.7	GERP -1.6, phastCons 1
Overall
CADD	8.253	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,578,406). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SLC4A4
Protein: p.Arg441=
Coding: c.1321C>A
MANE Select: NM_001098484
Type: single nucleotide variant
Location: chr4:71451300 (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

Disease context

autosomal recessive proximal renal tubular acidosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Proximal renal tubular acidosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: All ages

Similar variants

SLC4A4 p.Arg441Trp Uncertain significance ★★ ⚠ same residue
SLC4A4 c.1208+4A>C Uncertain significance ★★ same condition
SLC4A4 c.1322+5C>T Uncertain significance ★★ same condition
SLC4A4 c.*26G>T Uncertain significance ★★ same condition
SLC4A4 p.Ala454Thr Uncertain significance ★★ ⚠ same condition
SLC4A4 p.Ala454Val Uncertain significance ★★ ⚠ same condition
SLC4A4 p.Ala667Thr Uncertain significance ★★ ⚠ same condition
SLC4A4 p.Ala744Val Uncertain significance ★★ ⚠ 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/slc4a4-p-arg441 (accessed [today's date]).

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