Is SRP72 p.Pro568= (c.1704A>G) pathogenic?

SRP72 p.Pro568= (c.1704A>G) is classified Benign/Likely benign in SRP72 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-11-22). Ultra-rare (popmax 0.0667%, nfe); Associated with autosomal dominant aplasia and myelodysplasia.

What condition is associated with SRP72 p.Pro568= (c.1704A>G)?

SRP72 p.Pro568= (c.1704A>G) is associated with autosomal dominant aplasia and myelodysplasia (ClinVar).

How common is SRP72 p.Pro568= (c.1704A>G) in the general population?

SRP72 p.Pro568= (c.1704A>G) is ultra-rare (popmax 0.0667%, nfe) (gnomAD).

How is Autosomal dominant aplasia and myelodysplasia inherited?

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

SRP72 p.Pro568=

c.1704A>G · rs41280351 · VCV349133

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0667%, nfe)

Conditions

autosomal dominant aplasia and myelodysplasia

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 -0.78	GERP -3.5
Overall
CADD	6.377	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0667% European (non-Finnish) · 787/1,179,756 alleles

Filtering AF 0.0628% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0613%

Overall 0.0551% 889/1,613,694 alleles · ultra-rare exomes 802/1,461,408 · genomes 87/152,286 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0667%	1,499
Admixed American	0.0634%	1,578
Finnishnot grpmax-eligible	0.05%	2,001
Remaining individualsnot grpmax-eligible	0.0448%	2,231
African / African-American	0.004%	25,008
South Asian	0.0011%	91,030

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: SRP72
Protein: p.Pro568=
Coding: c.1704A>G
MANE Select: NM_006947
dbSNP: rs41280351
Type: single nucleotide variant
Location: chr4:56500561 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 82.76 · 7 PDB
Residue 568: the 'rna-binding' region; a turn; the 'disordered' region

Full SRP72 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant aplasia and myelodysplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant aplasia and myelodysplasia (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

SRP72 p.Pro568Gln Uncertain significance ★ ⚠ same residue
SRP72 p.Arg207His Uncertain significance ★★ ⚠ same condition
SRP72 p.Arg208Cys Uncertain significance ★★ ⚠ same condition
SRP72 p.Arg208His Uncertain significance ★★ ⚠ same condition
SRP72 p.Asn41Ser Uncertain significance ★★ ⚠ same condition
SRP72 p.Gln546Lys Uncertain significance ★★ ⚠ same condition
SRP72 p.Glu17Gly Uncertain significance ★★ ⚠ same condition
SRP72 p.Gly7Arg 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/srp72-p-pro568 (accessed [today's date]).

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