Is AGER p.Ala354= (c.1062C>T) pathogenic?

AGER p.Ala354= (c.1062C>T) is classified Likely benign in AGER (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). Ultra-rare (popmax 0.012%, afr).

How common is AGER p.Ala354= (c.1062C>T) in the general population?

AGER p.Ala354= (c.1062C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

AGER p.Ala354=

c.1062C>T · VCV4638936

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.272	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -3.2
Overall
CADD	2.135	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,908 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.000868% 14/1,613,386 alleles · ultra-rare exomes 10/1,461,168 · genomes 4/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,323
South Asian	0.0022%	45,540
Admixed American	0.00167%	59,918
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	8.48e-05%	1,179,800

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: AGER
Protein: p.Ala354=
Coding: c.1062C>T
MANE Select: NM_001136
Type: single nucleotide variant
Location: chr6:32181407 (GRCh38)
Gene constraint: LOEUF 1.068 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.74 · 33 PDB

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

Similar variants

AGER p.Ala19Gly Uncertain significance ★ ⚠ same type
AGER p.Ala355Thr Uncertain significance ★ ⚠ same type
AGER p.Ala375Ser Uncertain significance ★ ⚠ same type
AGER p.Ala41Val Uncertain significance ★ ⚠ same type
AGER p.Ala6Val Uncertain significance ★ ⚠ same type
AGER p.Ala76Val Uncertain significance ★ ⚠ same type
AGER p.Arg116Leu Uncertain significance ★ ⚠ same type
AGER p.Arg178Ser 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/ager-p-ala354 (accessed [today's date]).

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