Is ESF1 p.Phe323Leu (c.969T>G) pathogenic?

ESF1 p.Phe323Leu (c.969T>G) is classified Likely benign in ESF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-28). AlphaMissense: likely benign (0.2122); Absent from gnomAD v4.1.

How common is ESF1 p.Phe323Leu (c.969T>G) in the general population?

ESF1 p.Phe323Leu (c.969T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ESF1 p.Phe323Leu (c.969T>G)?

AlphaMissense predicts likely benign (score 0.2122) — an in-silico prediction, not a clinical call.

ESF1 p.Phe323Leu

c.969T>G · rs2516067953 · VCV2530565

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2122 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2122	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -4.42	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 3.8	GERP -0.23, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 68 kb · p 0.033 · regional, not allelic
Overall
CADD	14.9	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

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: ESF1
Protein: p.Phe323Leu
Coding: c.969T>G
MANE Select: NM_001276380
dbSNP: rs2516067953
Type: single nucleotide variant
Location: chr20:13775939 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.81
Residue 323: the 'disordered' region

Full ESF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NDUFAF5 c.-208C>T Benign ★★ same type
ESF1 p.Ala120Thr Uncertain significance ★ ⚠ same type
ESF1 p.Ala303Thr Uncertain significance ★ ⚠ same type
ESF1 p.Ala412Ser Uncertain significance ★ ⚠ same type
ESF1 p.Ala651Ser Uncertain significance ★ ⚠ same type
ESF1 p.Ala651Thr Uncertain significance ★ ⚠ same type
ESF1 p.Ala653Thr Uncertain significance ★ ⚠ same type
ESF1 p.Ala709Val 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/esf1-p-phe323leu (accessed [today's date]).

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