Is SLC4A11 p.Asn537= (c.1611C>T) pathogenic?

SLC4A11 p.Asn537= (c.1611C>T) is classified Benign in SLC4A11 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 12.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with corneal dystrophy.

SLC4A11 p.Asn537=

Q: What condition is associated with SLC4A11 p.Asn537= (c.1611C>T)?

SLC4A11 p.Asn537= (c.1611C>T) is associated with corneal dystrophy, corneal dystrophy-perceptive deafness syndrome, congenital hereditary endothelial dystrophy of cornea (ClinVar).

Q: How common is SLC4A11 p.Asn537= (c.1611C>T) in the general population?

SLC4A11 p.Asn537= (c.1611C>T) is common (popmax 12.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1611C>T · rs41281860 · VCV261997

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 12.6%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

corneal dystrophy

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 0.2	GERP -5, phastCons 0.003
Overall
CADD	3.561	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.6% European (non-Finnish) · 148,436/1,179,964 alleles

Filtering AF 12.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.5%

Overall 11.1% 178,482/1,613,742 alleles · common exomes 164,700/1,461,444 · genomes 13,782/152,298 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	14.2%	7
Ashkenazi Jewishnot grpmax-eligible	13.5%	7
European (non-Finnish)grpmax	12.6%	8
Remaining individualsnot grpmax-eligible	10.4%	10
Amishnot grpmax-eligible	9.76%	10
Admixed American	7.86%	13
Middle Eastern	7.36%	14
African / African-American	3.26%	31
South Asian	2.91%	34
East Asian	0.448%	223

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SLC4A11
Protein: p.Asn537=
Coding: c.1611C>T
MANE Select: NM_001174089
dbSNP: rs41281860
Type: single nucleotide variant
Location: chr20:3229655 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.36 · 4 PDB

Full SLC4A11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

corneal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: corneal dystrophy-perceptive deafness syndrome congenital hereditary endothelial dystrophy of cornea

Similar variants

SLC4A11 c.1168+1G>A Likely pathogenic ★★ same condition
SLC4A11 c.1282+1G>A Pathogenic/Likely pathogenic ★★ same condition
SLC4A11 c.1490-2A>G Likely pathogenic ★★ same condition
SLC4A11 c.1849+1G>A Likely pathogenic ★★ same condition
SLC4A11 c.2018+1G>A Likely pathogenic ★★ same condition
SLC4A11 c.2192+1G>A Pathogenic/Likely pathogenic ★★ same condition
SLC4A11 c.2389-1G>A Pathogenic/Likely pathogenic ★★ same condition
SLC4A11 c.2558+1G>A Pathogenic/Likely pathogenic ★★ 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/slc4a11-p-asn537 (accessed [today's date]).

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