Is ATG7 p.Pro577Ser (c.1729C>T) pathogenic?

ATG7 p.Pro577Ser (c.1729C>T) is classified Uncertain significance in ATG7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely pathogenic (0.9061); Very rare (popmax 0.0011%, sas).

How common is ATG7 p.Pro577Ser (c.1729C>T) in the general population?

ATG7 p.Pro577Ser (c.1729C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ATG7 p.Pro577Ser (c.1729C>T)?

AlphaMissense predicts likely pathogenic (score 0.9061) — an in-silico prediction, not a clinical call.

ATG7 p.Pro577Ser

c.1729C>T · VCV4164423

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9061 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9061	likely pathogenic
REVEL	0.609	indeterminate
SaProt	LLR -11.24	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 256 kb · p 0.014 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0011% South Asian · 1/91,066 alleles

Overall 6.2e-05% 1/1,614,058 alleles · very rare exomes 1/1,461,774 · genomes 0/152,284 · joint denominator

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: ATG7
Protein: p.Pro577Ser
Coding: c.1729C>T
MANE Select: NM_001349232
Type: single nucleotide variant
Location: chr3:11362858 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.06

Full ATG7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATG7 p.Arg659Ter Pathogenic/Likely pathogenic ★★ same type
ATG7 c.890-7C>T Benign ★★ same type
ATG7 c.890-8G>T Benign ★★ same type
ATG7 p.Ala530Thr Likely benign ★★ same type
ATG7 p.Glu291= Likely benign ★★ same type
ATG7 p.Lys326Gln Benign/Likely benign ★★ same type
ATG7 p.Pro426= Likely benign ★★ same type
ATG7 p.Val471Ala Benign/Likely benign ★★ ⚠ 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/atg7-p-pro577ser (accessed [today's date]).

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