Is SLC34A2 p.Pro44Ser (c.130C>T) pathogenic?

SLC34A2 p.Pro44Ser (c.130C>T) is classified Uncertain significance in SLC34A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.0783); Rare (popmax 0.107%, afr); Associated with Inborn genetic diseases.

What condition is associated with SLC34A2 p.Pro44Ser (c.130C>T)?

SLC34A2 p.Pro44Ser (c.130C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SLC34A2 p.Pro44Ser (c.130C>T) in the general population?

SLC34A2 p.Pro44Ser (c.130C>T) is rare (popmax 0.107%, afr) (gnomAD).

What do computational predictors say about SLC34A2 p.Pro44Ser (c.130C>T)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

SLC34A2 p.Pro44Ser

c.130C>T · rs147129009 · VCV2460146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.107%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.003	strongly benign-leaning
SaProt	LLR -5.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -2.9
Regional constraint	o/e 1.00	unconstrained · MANE · 14 kb · p 0.94 · regional, not allelic
Overall
CADD	0.477	PHRED · no single calibrated threshold — expert panels disagree

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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.107% African / African-American · 80/75,016 alleles

Filtering AF 0.0878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0808%

Overall 0.00613% 99/1,614,116 alleles · rare exomes 51/1,461,892 · genomes 48/152,224 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.107%	938
Admixed American	0.02%	5,002
Remaining individualsnot grpmax-eligible	0.008%	12,502
European (non-Finnish)	0.000169%	590,012

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: SLC34A2
Protein: p.Pro44Ser
Coding: c.130C>T
MANE Select: NM_006424
dbSNP: rs147129009
Type: single nucleotide variant
Location: chr4:25662722 (GRCh38)
Gene constraint: LOEUF 1.019 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.27

Full SLC34A2 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

SLC34A2 p.Pro44Arg Uncertain significance ★ ⚠ same residue
SLC34A2 p.Ala121Thr Uncertain significance ★★ ⚠ same condition
SLC34A2 p.Cys322Arg Uncertain significance ★★ ⚠ same condition
SLC34A2 p.Ile190Asn Uncertain significance ★★ ⚠ same condition
SLC34A2 p.Ile567Asn Uncertain significance ★★ ⚠ same condition
SLC34A2 p.Ser55Cys Uncertain significance ★★ ⚠ same condition
SLC34A2 p.Thr177Ala Uncertain significance ★★ ⚠ same condition
SLC34A2 p.Val167Asp 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/slc34a2-p-pro44ser (accessed [today's date]).

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