Is SLC4A11 p.Gly726Val (c.2177G>T) pathogenic?

SLC4A11 p.Gly726Val (c.2177G>T) is classified Uncertain significance in SLC4A11 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-03). AlphaMissense: likely pathogenic (0.9126); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SLC4A11 p.Gly726Val (c.2177G>T)?

SLC4A11 p.Gly726Val (c.2177G>T) is associated with Inborn genetic diseases (ClinVar).

How common is SLC4A11 p.Gly726Val (c.2177G>T) in the general population?

SLC4A11 p.Gly726Val (c.2177G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SLC4A11 p.Gly726Val (c.2177G>T)?

AlphaMissense predicts likely pathogenic (score 0.9126) — an in-silico prediction, not a clinical call.

SLC4A11 p.Gly726Val

c.2177G>T · VCV4864637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9126 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9126	likely pathogenic
REVEL	0.818	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 5,727 bp · p 0.0019 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM G742V vs ClinVar G726V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SLC4A11
Protein: p.Gly726Val
Coding: c.2177G>T
MANE Select: NM_001174089
Type: single nucleotide variant
Location: chr20:3228853 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SLC4A11 p.Gly726Arg Uncertain significance ★★ ⚠ same residue
SLC4A11 p.Gly726= Likely benign ★ same residue
SLC4A11 p.Arg714Ter Pathogenic ★★ same condition
SLC4A11 p.Ala121Ser Uncertain significance ★★ same condition
SLC4A11 p.Ala249Val Uncertain significance ★★ same condition
SLC4A11 p.Ala420Thr Uncertain significance ★★ same condition
SLC4A11 p.Arg142His Uncertain significance ★★ ⚠ same condition
SLC4A11 p.Arg211Trp 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/slc4a11-p-gly726val (accessed [today's date]).

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