Is AGGF1 p.Pro262Leu (c.785C>T) pathogenic?

AGGF1 p.Pro262Leu (c.785C>T) is classified Uncertain significance in AGGF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-30). AlphaMissense: likely benign (0.0705); Very rare (popmax 0.00224%, eas).

How common is AGGF1 p.Pro262Leu (c.785C>T) in the general population?

AGGF1 p.Pro262Leu (c.785C>T) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about AGGF1 p.Pro262Leu (c.785C>T)?

AlphaMissense predicts likely benign (score 0.0705) — an in-silico prediction, not a clinical call.

AGGF1 p.Pro262Leu

c.785C>T · VCV3275937

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0705 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0705	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -7.96	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 9.3	GERP 1.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 27 kb · p 0.39 · regional, not allelic
Overall
CADD	23.8	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 0.00224% East Asian · 1/44,742 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000868% 14/1,612,748 alleles · very rare exomes 13/1,460,870 · genomes 1/151,878 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,742
South Asian	0.0022%	45,472
African / African-American	0.00134%	74,766
European (non-Finnish)	0.000848%	117,942

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: AGGF1
Protein: p.Pro262Leu
Coding: c.785C>T
MANE Select: NM_018046
Type: single nucleotide variant
Location: chr5:77039634 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.24
Residue 262: the 'disordered' region

Full AGGF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGGF1 p.Pro262Ser Uncertain significance ★ ⚠ same residue
AGGF1 c.313+6T>C Benign ★★ same type
AGGF1 p.Glu133Lys Benign/Likely benign ★★ same type
AGGF1 p.Met706Leu Benign ★★ same type
AGGF1 p.Tyr112Cys Likely benign ★★ same type
AGGF1 p.Tyr382= Benign/Likely benign ★★ same type
AGGF1 p.Ala314Thr Uncertain significance ★ ⚠ same type
AGGF1 p.Ala385Val 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/aggf1-p-pro262leu (accessed [today's date]).

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