Is AFTPH p.Pro908Arg (c.2723C>G) pathogenic?

AFTPH p.Pro908Arg (c.2723C>G) is classified Uncertain significance in AFTPH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: likely pathogenic (0.938); Absent from gnomAD v4.1.

How common is AFTPH p.Pro908Arg (c.2723C>G) in the general population?

AFTPH p.Pro908Arg (c.2723C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFTPH p.Pro908Arg (c.2723C>G)?

AlphaMissense predicts likely pathogenic (score 0.938) — an in-silico prediction, not a clinical call.

AFTPH p.Pro908Arg

c.2723C>G · VCV4638792

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.938 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.938	likely pathogenic · top 6% in AFTPH
REVEL	0.689	pathogenic-leaning
SaProt	LLR -8.09	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Overall
CADD	25.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AFTPH
Protein: p.Pro908Arg
Coding: c.2723C>G
MANE Select: NM_203437
Type: single nucleotide variant
Location: chr2:64591947 (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-pro908arg (accessed [today's date]).

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