Is AFTPH p.Glu894Asp (c.2682G>T) pathogenic?

AFTPH p.Glu894Asp (c.2682G>T) is classified Uncertain significance in AFTPH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). AlphaMissense: ambiguous (0.4739); Very rare (popmax 0.00167%, amr).

How common is AFTPH p.Glu894Asp (c.2682G>T) in the general population?

AFTPH p.Glu894Asp (c.2682G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about AFTPH p.Glu894Asp (c.2682G>T)?

AlphaMissense predicts ambiguous (score 0.4739) — an in-silico prediction, not a clinical call.

AFTPH p.Glu894Asp

c.2682G>T · VCV3505119

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4739 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4739	ambiguous
REVEL	0.126	moderately benign-leaning
SaProt	LLR -6.73	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 0.87	GERP -0.95, phastCons 1
Overall
CADD	21.3	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 0.00167% Admixed American · 1/60,000 alleles

Overall 6.84e-05% 1/1,461,694 alleles · very rare

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: AFTPH
Protein: p.Glu894Asp
Coding: c.2682G>T
MANE Select: NM_203437
Type: single nucleotide variant
Location: chr2:64591906 (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.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
AFTPH p.Arg256Thr Uncertain significance ★ ⚠ same type
AFTPH p.Arg262Trp 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-glu894asp (accessed [today's date]).

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