Is AGFG2 p.Phe249Ser (c.746T>C) pathogenic?

AGFG2 p.Phe249Ser (c.746T>C) is classified Uncertain significance in AGFG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-01). AlphaMissense: likely benign (0.2767); Absent from gnomAD v4.1.

How common is AGFG2 p.Phe249Ser (c.746T>C) in the general population?

AGFG2 p.Phe249Ser (c.746T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGFG2 p.Phe249Ser (c.746T>C)?

AlphaMissense predicts likely benign (score 0.2767) — an in-silico prediction, not a clinical call.

AGFG2 p.Phe249Ser

c.746T>C · VCV4897081

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2767 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2767	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 3.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 26 kb · p 0.18 · regional, not allelic
Overall
CADD	23.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGFG2
Protein: p.Phe249Ser
Coding: c.746T>C
MANE Select: NM_006076
Type: single nucleotide variant
Location: chr7:100554253 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 59.26

Full AGFG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGFG2 p.Ala221Pro Uncertain significance ★ ⚠ same type
AGFG2 p.Ala236Thr Uncertain significance ★ ⚠ same type
AGFG2 p.Ala280Thr Uncertain significance ★ ⚠ same type
AGFG2 p.Ala373Ser Uncertain significance ★ ⚠ same type
AGFG2 p.Ala389Val Uncertain significance ★ ⚠ same type
AGFG2 p.Ala414Thr Uncertain significance ★ ⚠ same type
AGFG2 p.Ala414Val Uncertain significance ★ ⚠ same type
AGFG2 p.Ala51Val 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/agfg2-p-phe249ser (accessed [today's date]).

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