Is AGER p.Pro71Thr (c.211C>A) pathogenic?

AGER p.Pro71Thr (c.211C>A) is classified Uncertain significance in AGER (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely benign (0.0795); Very rare (popmax 0.00133%, afr).

How common is AGER p.Pro71Thr (c.211C>A) in the general population?

AGER p.Pro71Thr (c.211C>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about AGER p.Pro71Thr (c.211C>A)?

AlphaMissense predicts likely benign (score 0.0795) — an in-silico prediction, not a clinical call.

AGER p.Pro71Thr

c.211C>A · VCV3506527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0795 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0795	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -9.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -2.9, phastCons 0.031
Regional constraint	o/e 0.95	unconstrained · MANE · 3,076 bp · p 0.25 · regional, not allelic
Overall
CADD	15.01	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00133% African / African-American · 1/75,050 alleles

Overall 0.000124% 2/1,613,110 alleles · very rare exomes 2/1,460,772 · genomes 0/152,338 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,050
European (non-Finnish)	8.47e-05%	1,180,038

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.Pro71Thr
Coding: c.211C>A
MANE Select: NM_001136
Type: single nucleotide variant
Location: chr6:32183699 (GRCh38)
Gene constraint: LOEUF 1.068 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.74 · 33 PDB
Residue 71: an α-helix; the ig-like v-type domain

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-pro71thr (accessed [today's date]).

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