Is AJAP1 p.Ser172Arg (c.516C>G) pathogenic?

AJAP1 p.Ser172Arg (c.516C>G) is classified Uncertain significance in AJAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). AlphaMissense: ambiguous (0.4385); Very rare (popmax 0.00376%, amr).

How common is AJAP1 p.Ser172Arg (c.516C>G) in the general population?

AJAP1 p.Ser172Arg (c.516C>G) is very rare (popmax 0.00376%, amr) (gnomAD).

What do computational predictors say about AJAP1 p.Ser172Arg (c.516C>G)?

AlphaMissense predicts ambiguous (score 0.4385) — an in-silico prediction, not a clinical call.

AJAP1 p.Ser172Arg

c.516C>G · rs1340787438 · VCV2209606

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4385 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00376%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4385	ambiguous
REVEL	0.114	moderately benign-leaning
SaProt	LLR -6.79	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.95	GERP -0.85, phastCons 0.77
Regional constraint	o/e 1.03	unconstrained · MANE · 119 kb · p 0.53 · regional, not allelic
Overall
CADD	18.9	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 0.00376% Admixed American · 2/53,258 alleles

Filtering AF 0.000623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000233%

Overall 0.000644% 10/1,553,630 alleles · very rare exomes 10/1,401,342 · genomes 0/152,288 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00376%	26,629
European (non-Finnish)	0.000697%	143,543

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: AJAP1
Protein: p.Ser172Arg
Coding: c.516C>G
MANE Select: NM_018836
dbSNP: rs1340787438
Type: single nucleotide variant
Location: chr1:4712386 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.22
Residue 172: the 'disordered' region

Full AJAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AJAP1 p.Pro228Arg Uncertain significance ★★ ⚠ same type
AJAP1 p.Ser260Gly Uncertain significance ★★ ⚠ same type
AJAP1 p.Ala35Val Benign ★★ same type
AJAP1 p.Gly202Asp Benign ★★ same type
AJAP1 p.Ala115Thr Uncertain significance ★ ⚠ same type
AJAP1 p.Ala122Thr Uncertain significance ★ ⚠ same type
AJAP1 p.Ala123Thr Uncertain significance ★ ⚠ same type
AJAP1 p.Ala142Val 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/ajap1-p-ser172arg (accessed [today's date]).

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