Is ALKBH4 p.Pro207Ser (c.619C>T) pathogenic?

ALKBH4 p.Pro207Ser (c.619C>T) is classified Uncertain significance in ALKBH4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-25). AlphaMissense: likely benign (0.0844); Very rare (popmax 0.00865%, nfe).

How common is ALKBH4 p.Pro207Ser (c.619C>T) in the general population?

ALKBH4 p.Pro207Ser (c.619C>T) is very rare (popmax 0.00865%, nfe) (gnomAD).

What do computational predictors say about ALKBH4 p.Pro207Ser (c.619C>T)?

AlphaMissense predicts likely benign (score 0.0844) — an in-silico prediction, not a clinical call.

ALKBH4 p.Pro207Ser

c.619C>T · rs757496182 · VCV2464042

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0844 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00865%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0844	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -7.46	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 5.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,439 bp · p 0.19 · regional, not allelic
Overall
CADD	14.04	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

Grpmax group 0.00865% European (non-Finnish) · 100/1,156,498 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00673%

Overall 0.00681% 106/1,557,030 alleles · very rare exomes 101/1,404,818 · genomes 5/152,212 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00865%	11,565
Remaining individualsnot grpmax-eligible	0.00495%	20,189
African / African-American	0.00406%	24,617

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: ALKBH4
Protein: p.Pro207Ser
Coding: c.619C>T
MANE Select: NM_017621
dbSNP: rs757496182
Type: single nucleotide variant
Location: chr7:102457684 (GRCh38)
Gene constraint: LOEUF 1.035 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.14
Residue 207: the fe2og dioxygenase domain

Full ALKBH4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALKBH4 p.Pro207Leu Uncertain significance ★ ⚠ same residue
ALKBH4 p.Ala238Thr Uncertain significance ★ ⚠ same type
ALKBH4 p.Ala238Val Uncertain significance ★ ⚠ same type
ALKBH4 p.Ala41Val Uncertain significance ★ ⚠ same type
ALKBH4 p.Ala4Pro Uncertain significance ★ ⚠ same type
ALKBH4 p.Ala4Thr Uncertain significance ★ ⚠ same type
ALKBH4 p.Ala6Thr Uncertain significance ★ ⚠ same type
ALKBH4 p.Arg104Gln 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/alkbh4-p-pro207ser (accessed [today's date]).

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