Is ATG16L1 p.Val593= (c.1779C>T) pathogenic?

ATG16L1 p.Val593= (c.1779C>T) is classified Likely benign in ATG16L1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-24). Ultra-rare (popmax 0.0164%, mid); Associated with ATG16L1-related disorder.

What condition is associated with ATG16L1 p.Val593= (c.1779C>T)?

ATG16L1 p.Val593= (c.1779C>T) is associated with ATG16L1-related disorder (ClinVar).

How common is ATG16L1 p.Val593= (c.1779C>T) in the general population?

ATG16L1 p.Val593= (c.1779C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

ATG16L1 p.Val593=

c.1779C>T · rs199749659 · VCV3039220

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

ATG16L1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.203	benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP 1.6, phastCons 1
Overall
CADD	6.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00409% 66/1,613,368 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.125%	800
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.00961%	10,411
Admixed American	0.00834%	11,986
European (non-Finnish)	0.00144%	69,400

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ATG16L1
Protein: p.Val593=
Coding: c.1779C>T
MANE Select: NM_030803
dbSNP: rs199749659
Type: single nucleotide variant
Location: chr2:233294305 (GRCh38)
Gene constraint: LOEUF 0.545 · pLI 0.27 (gnomAD)
Structure: AlphaFold pLDDT 84.15 · 16 PDB
Residue 593: a β-strand

Full ATG16L1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ATG16L1-related disorder

Similar variants

ATG16L1 p.Arg219Gln Likely benign same condition
ATG16L1 p.Gln20= Likely benign same condition
ATG16L1 p.His428= Likely benign same condition
ATG16L1 p.Thr184= Likely benign same condition
ATG16L1 p.Asp596= Benign ★★ same type
ATG16L1 p.Thr300Ala Benign ★★ same type
ATG16L1 p.Ala263Val Uncertain significance ★ ⚠ same type
ATG16L1 p.Ala384Thr 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/atg16l1-p-val593 (accessed [today's date]).

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