Is RECQL4 p.Ser92Phe (c.275C>T) pathogenic?

RECQL4 p.Ser92Phe (c.275C>T) is classified Benign in RECQL4 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-01). AlphaMissense: likely benign (0.1067); Low-frequency (popmax 2.98%, afr).

How common is RECQL4 p.Ser92Phe (c.275C>T) in the general population?

RECQL4 p.Ser92Phe (c.275C>T) is low-frequency (popmax 2.98%, afr) (gnomAD).

What do computational predictors say about RECQL4 p.Ser92Phe (c.275C>T)?

AlphaMissense predicts likely benign (score 0.1067) — an in-silico prediction, not a clinical call.

RECQL4 p.Ser92Phe

c.275C>T · rs200516441 · VCV197231

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1067 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.98%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.1067	likely benign
SaProt	LLR -8.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -3.2, phastCons 0.27
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	10.25	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.98% African / African-American · 2,240/75,068 alleles

Filtering AF 2.88% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.84%

Overall 0.155% 2,494/1,612,184 alleles · low-frequency exomes 1,254/1,459,808 · genomes 1,240/152,376 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.98%	34
Admixed American	0.167%	600
Remaining individualsnot grpmax-eligible	0.163%	612
Middle Eastern	0.116%	865
European (non-Finnish)	0.00364%	27,435
South Asian	0.0022%	45,523

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.Ser92Phe
Coding: c.275C>T
MANE Select: NM_004260
dbSNP: rs200516441
Type: single nucleotide variant
Location: chr8:144517129 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 92: a UniProt-annotated variant site (in); the 'disordered' region

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

Similar variants

RECQL4 p.Ser92Pro Benign ★★ same residue
RECQL4 p.Ser92= Benign ★ same residue
RECQL4 p.Ser92Arg Uncertain significance ★ same residue
RECQL4 p.Ser92Leu Benign ★ same residue
RECQL4 c.1132-1G>A Likely pathogenic ★★ same type
RECQL4 c.1259-1G>A Pathogenic/Likely pathogenic ★★ same type
RECQL4 c.1391-1G>A Pathogenic ★★ same type
RECQL4 c.1704+1G>A Pathogenic/Likely pathogenic ★★ 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/recql4-p-ser92phe (accessed [today's date]).

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