Is APLN p.Ser16Tyr (c.47C>A) pathogenic?

APLN p.Ser16Tyr (c.47C>A) is classified Uncertain significance in APLN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-23). AlphaMissense: likely benign (0.2657); Absent from gnomAD v4.1.

How common is APLN p.Ser16Tyr (c.47C>A) in the general population?

APLN p.Ser16Tyr (c.47C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APLN p.Ser16Tyr (c.47C>A)?

AlphaMissense predicts likely benign (score 0.2657) — an in-silico prediction, not a clinical call.

APLN p.Ser16Tyr

c.47C>A · rs757960178 · VCV2303435

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2657 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,157,163)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2657	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -8.78	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 3.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 6,001 bp · p 0.23 · regional, not allelic
Overall
CADD	17.52	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

No allele count reported in gnomAD v4.1 (AN 1,157,163). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: APLN
Protein: p.Ser16Tyr
Coding: c.47C>A
MANE Select: NM_017413
dbSNP: rs757960178
Type: single nucleotide variant
Location: chrX:129654584 (GRCh38)
Structure: AlphaFold pLDDT 67.45 · 5 PDB

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

Similar variants

APLN c.67+151A>G Benign ★★ same type
APLN c.-107T>C Benign ★★ same type
APLN c.-314T>C Benign ★★ same type
APLN c.*5+62C>T Benign ★★ same type
APLN p.Arg49Trp Uncertain significance ★ ⚠ same type
APLN p.Arg59Gln Uncertain significance ★ ⚠ same type
APLN p.Arg59Trp Uncertain significance ★ ⚠ same type
APLN p.Arg63His 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/apln-p-ser16tyr (accessed [today's date]).

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