Is AGFG1 p.Pro511= (c.1533C>T) pathogenic?

AGFG1 p.Pro511= (c.1533C>T) is classified Likely benign in AGFG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). Ultra-rare (popmax 0.0329%, mid).

How common is AGFG1 p.Pro511= (c.1533C>T) in the general population?

AGFG1 p.Pro511= (c.1533C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

AGFG1 p.Pro511=

c.1533C>T · rs529173258 · VCV2651962

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.674	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.084	GERP 0.24, phastCons 0.52
Overall
CADD	11.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00347% 56/1,614,018 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	0.00398%	25,107
Admixed American	0.00333%	29,999
African / African-American	0.00133%	74,914

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: AGFG1
Protein: p.Pro511=
Coding: c.1533C>T
MANE Select: NM_004504
dbSNP: rs529173258
Type: single nucleotide variant
Location: chr2:227552113 (GRCh38)
Gene constraint: LOEUF 0.286 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 57.58 · 3 PDB

Full AGFG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGFG1 c.814+955G>A Uncertain significance ★ same type
AGFG1 p.Ala210Val Uncertain significance ★ ⚠ same type
AGFG1 p.Ala241Val Uncertain significance ★ ⚠ same type
AGFG1 p.Ala355Pro Uncertain significance ★ ⚠ same type
AGFG1 p.Ala438Gly Uncertain significance ★ ⚠ same type
AGFG1 p.Ala439Val Uncertain significance ★ ⚠ same type
AGFG1 p.Arg186Leu Uncertain significance ★ ⚠ same type
AGFG1 p.Asn228Ser Uncertain significance ★ ⚠ 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/agfg1-p-pro511 (accessed [today's date]).

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