Is AFTPH p.Ser674Ala (c.2020T>G) pathogenic?

AFTPH p.Ser674Ala (c.2020T>G) is classified Uncertain significance in AFTPH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-12). AlphaMissense: likely benign (0.0909); Absent from gnomAD v4.1.

How common is AFTPH p.Ser674Ala (c.2020T>G) in the general population?

AFTPH p.Ser674Ala (c.2020T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFTPH p.Ser674Ala (c.2020T>G)?

AlphaMissense predicts likely benign (score 0.0909) — an in-silico prediction, not a clinical call.

AFTPH p.Ser674Ala

c.2020T>G · rs766477381 · VCV2282841

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0909 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0909	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -7.67	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 6.2	GERP 0.63, phastCons 1
Overall
CADD	23.6	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

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.Ser674Ala
Coding: c.2020T>G
MANE Select: NM_203437
dbSNP: rs766477381
Type: single nucleotide variant
Location: chr2:64567646 (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-ser674ala (accessed [today's date]).

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