Is AFTPH p.Thr620Ala (c.1858A>G) pathogenic?

AFTPH p.Thr620Ala (c.1858A>G) is classified Likely benign in AFTPH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-01). AlphaMissense: likely benign (0.0834); Rare (popmax 0.726%, mid).

How common is AFTPH p.Thr620Ala (c.1858A>G) in the general population?

AFTPH p.Thr620Ala (c.1858A>G) is rare (popmax 0.726%, mid) (gnomAD).

What do computational predictors say about AFTPH p.Thr620Ala (c.1858A>G)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

AFTPH p.Thr620Ala

c.1858A>G · rs34934815 · VCV2651002

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.726%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.36	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 4.2	GERP 0.79, phastCons 1
Overall
CADD	11.98	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 0.726% Middle Eastern · 44/6,058 alleles

Filtering AF 0.556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.496%

Overall 0.359% 5,796/1,613,868 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.726%	138
Ashkenazi Jewishnot grpmax-eligible	0.723%	138
Admixed American	0.433%	231
European (non-Finnish)	0.415%	241
Remaining individualsnot grpmax-eligible	0.381%	263
African / African-American	0.0747%	1,339
South Asian	0.0736%	1,358
Finnishnot grpmax-eligible	0.0344%	2,910

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.Thr620Ala
Coding: c.1858A>G
MANE Select: NM_203437
dbSNP: rs34934815
Type: single nucleotide variant
Location: chr2:64553332 (GRCh38)
Gene constraint: LOEUF 0.207 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.36
Residue 620: the 'disordered' region

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

Similar variants

AFTPH p.Thr620Met Likely benign ★ ⚠ 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
AFTPH p.Arg256Thr 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-thr620ala (accessed [today's date]).

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