Is AFTPH p.Asp26Ala (c.77A>C) pathogenic?

AFTPH p.Asp26Ala (c.77A>C) is classified Uncertain significance in AFTPH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: ambiguous (0.4419); Absent from gnomAD v4.1.

How common is AFTPH p.Asp26Ala (c.77A>C) in the general population?

AFTPH p.Asp26Ala (c.77A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFTPH p.Asp26Ala (c.77A>C)?

AlphaMissense predicts ambiguous (score 0.4419) — an in-silico prediction, not a clinical call.

AFTPH p.Asp26Ala

c.77A>C · rs2545217964 · VCV2301058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4419 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4419	ambiguous
REVEL	0.283	benign-leaning
SaProt	LLR -10.43	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.3	GERP 1.9, phastCons 1
Overall
CADD	26.4	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.Asp26Ala
Coding: c.77A>C
MANE Select: NM_203437
dbSNP: rs2545217964
Type: single nucleotide variant
Location: chr2:64551551 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.36
Residue 26: the 'interaction with ap1g1, ap1g2, gga1 and gga3' region; the 'disordered' region

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-asp26ala (accessed [today's date]).

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