Is AFG1L p.Phe379Val (c.1135T>G) pathogenic?

AFG1L p.Phe379Val (c.1135T>G) is classified Uncertain significance in AFG1L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: ambiguous (0.4193); Absent from gnomAD v4.1.

How common is AFG1L p.Phe379Val (c.1135T>G) in the general population?

AFG1L p.Phe379Val (c.1135T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFG1L p.Phe379Val (c.1135T>G)?

AlphaMissense predicts ambiguous (score 0.4193) — an in-silico prediction, not a clinical call.

AFG1L p.Phe379Val

c.1135T>G · VCV3504372

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4193 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4193	ambiguous
REVEL	0.306	indeterminate
SaProt	LLR -10.95	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 227 kb · p 0.14 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

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: AFG1L
Protein: p.Phe379Val
Coding: c.1135T>G
MANE Select: NM_145315
Type: single nucleotide variant
Location: chr6:108510284 (GRCh38)
Gene constraint: LOEUF 1.018 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.92

Full AFG1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AFG1L p.Ala2Val Uncertain significance ★ ⚠ same type
AFG1L p.Ala305Thr Uncertain significance ★ ⚠ same type
AFG1L p.Ala339Gly Uncertain significance ★ ⚠ same type
AFG1L p.Ala60Pro Uncertain significance ★ ⚠ same type
AFG1L p.Arg12Ser Uncertain significance ★ ⚠ same type
AFG1L p.Arg160Trp Uncertain significance ★ ⚠ same type
AFG1L p.Arg176Cys Uncertain significance ★ ⚠ same type
AFG1L p.Arg176His 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/afg1l-p-phe379val (accessed [today's date]).

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