Is AADACL2 p.Phe50Ser (c.149T>C) pathogenic?

AADACL2 p.Phe50Ser (c.149T>C) is classified Uncertain significance in AADACL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-22). AlphaMissense: likely benign (0.2684); Ultra-rare (popmax 0.0134%, eas).

How common is AADACL2 p.Phe50Ser (c.149T>C) in the general population?

AADACL2 p.Phe50Ser (c.149T>C) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about AADACL2 p.Phe50Ser (c.149T>C)?

AlphaMissense predicts likely benign (score 0.2684) — an in-silico prediction, not a clinical call.

AADACL2 p.Phe50Ser

c.149T>C · rs202223368 · VCV2348648

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2684 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2684	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -10.99	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.62, phastCons 0.43
Regional constraint	o/e 0.97	unconstrained · MANE · 23 kb · p 0.62 · regional, not allelic
Overall
CADD	18.66	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

Grpmax group 0.0134% East Asian · 6/44,704 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00395%

Overall 0.000498% 8/1,607,292 alleles · ultra-rare exomes 7/1,454,934 · genomes 1/152,358 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,451
Remaining individualsnot grpmax-eligible	0.00321%	31,112

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: AADACL2
Protein: p.Phe50Ser
Coding: c.149T>C
MANE Select: NM_207365
dbSNP: rs202223368
Type: single nucleotide variant
Location: chr3:151740656 (GRCh38)
Gene constraint: LOEUF 1.529 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.42

Full AADACL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AADACL2 p.Ala148Thr Uncertain significance ★ ⚠ same type
AADACL2 p.Ala186Val Uncertain significance ★ ⚠ same type
AADACL2 p.Ala197Gly Uncertain significance ★ ⚠ same type
AADACL2 p.Ala197Val Uncertain significance ★ ⚠ same type
AADACL2 p.Ala322Val Uncertain significance ★ ⚠ same type
AADACL2 p.Ala373Asp Uncertain significance ★ ⚠ same type
AADACL2 p.Ala373Val Uncertain significance ★ ⚠ same type
AADACL2 p.Arg105Gln 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/aadacl2-p-phe50ser (accessed [today's date]).

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