Is AFTPH p.Ser839Tyr (c.2516C>A) pathogenic?

AFTPH p.Ser839Tyr (c.2516C>A) is classified Uncertain significance in AFTPH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: ambiguous (0.3689); Absent from gnomAD v4.1.

How common is AFTPH p.Ser839Tyr (c.2516C>A) in the general population?

AFTPH p.Ser839Tyr (c.2516C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFTPH p.Ser839Tyr (c.2516C>A)?

AlphaMissense predicts ambiguous (score 0.3689) — an in-silico prediction, not a clinical call.

AFTPH p.Ser839Tyr

c.2516C>A · VCV4638788

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3689 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,599,238)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3689	ambiguous
REVEL	0.226	benign-leaning
SaProt	LLR -9.20	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 3.4	GERP 1.2, phastCons 1
Overall
CADD	26.0	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

No allele count reported in gnomAD v4.1 (AN 1,599,238). 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: AFTPH
Protein: p.Ser839Tyr
Coding: c.2516C>A
MANE Select: NM_203437
Type: single nucleotide variant
Location: chr2:64581250 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.36

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

Similar variants

AFTPH p.Ser839Phe Uncertain significance ★ ⚠ same residue
AFTPH p.Ser839Thr Uncertain significance ★ ⚠ same residue
AFTPH p.Ala204Thr Uncertain significance ★ ⚠ same type
AFTPH p.Ala20Gly Uncertain significance ★ ⚠ same type
AFTPH p.Ala526Gly Uncertain significance ★ ⚠ same type
AFTPH p.Ala587Thr Uncertain significance ★ ⚠ same type
AFTPH p.Ala658Thr Uncertain significance ★ ⚠ same type
AFTPH p.Ala905Thr 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/aftph-p-ser839tyr (accessed [today's date]).

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