Is RECQL4 p.Phe342= (c.1026C>T) pathogenic?

RECQL4 p.Phe342= (c.1026C>T) is classified Likely benign in RECQL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with RECQL4 p.Phe342= (c.1026C>T)?

RECQL4 p.Phe342= (c.1026C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RECQL4 p.Phe342= (c.1026C>T) in the general population?

RECQL4 p.Phe342= (c.1026C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

RECQL4 p.Phe342=

c.1026C>T · VCV3787966

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.75	GERP -2.4
Overall
CADD	0.791	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,092 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00031% 5/1,612,766 alleles · very rare exomes 5/1,460,406 · genomes 0/152,360 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,364
European (non-Finnish)	0.00017%	589,932

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: RECQL4
Protein: p.Phe342=
Coding: c.1026C>T
MANE Select: NM_004260
Type: single nucleotide variant
Location: chr8:144516093 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB

Full RECQL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RECQL4 p.Phe342Leu Uncertain significance ★ ⚠ same residue
RECQL4 p.Phe342Ser Uncertain significance ★ ⚠ same residue
RECQL4 p.Ala1001Thr Uncertain significance ★★ ⚠ same condition
RECQL4 p.Ala1066Thr Uncertain significance ★★ ⚠ same condition
RECQL4 p.Ala1174Pro Uncertain significance ★★ ⚠ same condition
RECQL4 p.Ala122Ser Uncertain significance ★★ ⚠ same condition
RECQL4 p.Ala152Gly Uncertain significance ★★ ⚠ same condition
RECQL4 p.Ala152Thr Uncertain significance ★★ ⚠ same condition

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/recql4-p-phe342 (accessed [today's date]).

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