Is SARDH p.Pro433= (c.1299G>A) pathogenic?

SARDH p.Pro433= (c.1299G>A) is classified Benign/Likely benign in SARDH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-10-08). Low-frequency (popmax 1.25%, afr); Associated with sarcosinemia.

What condition is associated with SARDH p.Pro433= (c.1299G>A)?

SARDH p.Pro433= (c.1299G>A) is associated with sarcosinemia (ClinVar).

How common is SARDH p.Pro433= (c.1299G>A) in the general population?

SARDH p.Pro433= (c.1299G>A) is low-frequency (popmax 1.25%, afr) (gnomAD).

How is Sarcosinemia inherited?

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

SARDH p.Pro433=

c.1299G>A · rs147188337 · VCV711531

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.25%, afr)

Conditions

sarcosinemia

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 -12	GERP -2.1
Overall
CADD	1.369	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.25% African / African-American · 934/74,988 alleles

Filtering AF 1.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.15%

Overall 0.0683% 1,100/1,610,338 alleles · low-frequency exomes 578/1,458,178 · genomes 522/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.25%	80
Remaining individualsnot grpmax-eligible	0.0928%	1,077
Admixed American	0.0667%	1,500
Middle Eastern	0.066%	1,516
East Asian	0.0647%	1,547
South Asian	0.0165%	6,071
European (non-Finnish)	0.00169%	58,998

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: SARDH
Protein: p.Pro433=
Coding: c.1299G>A
MANE Select: NM_001134707
dbSNP: rs147188337
Type: single nucleotide variant
Location: chr9:133712648 (GRCh38)
Gene constraint: LOEUF 1.088 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.03

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

Disease context

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

For Sarcosinemia (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

SARDH p.Pro433Leu Uncertain significance ★ ⚠ same residue
SARDH p.Gly526Ala Uncertain significance ★★ ⚠ same condition
SARDH p.Thr145Met Uncertain significance ★★ ⚠ same condition
SARDH p.Asn158Ser Benign ★★ same condition
SARDH p.Ala793Val Uncertain significance ★ ⚠ same condition
SARDH p.Arg481His Uncertain significance ★ ⚠ same condition
SARDH p.Asp436fs Likely pathogenic ★ same condition
SARDH c.1471-8C>T Benign ★★ 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/sardh-p-pro433 (accessed [today's date]).

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